Showing papers on "Bromodomain published in 2005"
TL;DR: Proteomic analysis revealed that Brd4 interacts with cyclinT1 and Cdk9 that constitutes core positive transcription elongation factor b (P-TEFb) and is a positive regulatory component of P- TEFb, which alternately interacts with Brd 4 and the inhibitory subunit to maintain functional equilibrium in the cell.
1,120 citations
TL;DR: It is shown that in stress-induced cells, the 7SK/HEXIM1-bound P-TEFb is quantitatively converted into the Brd4-associated form, which is necessary to form the transcriptionally active P-teFb, recruits P- TEFb to a promoter, and enables P-TFb to contact the Mediator complex, a potential target for the Br d4-mediated recruitment.
1,016 citations
TL;DR: The SET-domain protein methyltransferase superfamily includes all but one of the proteins known to methylate histones on lysine.
Abstract: The SET-domain protein methyltransferase superfamily includes all but one of the proteins known to methylate histones on lysine. Histone methylation is important in the regulation of chromatin and gene expression.
718 citations
TL;DR: In S. cerevisiae, histone variant H2A.Z is deposited in euchromatin at the flanks of silent heterochromatin to prevent its ectopic spread and enrichment at 5' ends is observed not only at actively transcribed genes but also at inactive loci.
710 citations
TL;DR: It is found that reduction in the levels of hMSLs and acetylation of H4 at lysine 16 are correlated with reduced transcription of some genes and with a G2/M cell cycle arrest.
Abstract: We describe a stable, multisubunit human histone acetyltransferase complex (hMSL) that contains homologs of the Drosophila dosage compensation proteins MOF, MSL1, MSL2, and MSL3. This complex shows strong specificity for histone H4 lysine 16 in chromatin in vitro, and RNA interference-mediated knockdown experiments reveal that it is responsible for the majority of H4 acetylation at lysine 16 in the cell. We also find that hMOF is a component of additional complexes, forming associations with host cell factor 1 and a protein distantly related to MSL1 (hMSL1v1). We find two versions of hMSL3 in the hMSL complex that differ by the presence of the chromodomain. Lastly, we find that reduction in the levels of hMSLs and acetylation of H4 at lysine 16 are correlated with reduced transcription of some genes and with a G2/M cell cycle arrest. This is of particular interest given the recent correlation of global loss of acetylation of lysine 16 in histone H4 with tumorigenesis.
311 citations
TL;DR: Post-translational modification is a major mechanism by which protein function is regulated in eukaryotes and coordinates intermolecular and intramolecular signaling for the qualitative and quantitative control of protein function in vivo.
Abstract: Post-translational modification is a major mechanism by which protein function is regulated in eukaryotes. Instead of single-site action, many proteins such as histones, p53, RNA polymerase II, tubulin, Cdc25C and tyrosine kinases are modified at multiple sites by modifications like phosphorylation, acetylation, methylation, ubiquitination, sumoylation and citrullination. Multisite modification on a protein constitutes a complex regulatory program that resembles a dynamic 'molecular barcode' and transduces molecular information to and from signaling pathways. This program imparts effects through 'loss-of-function' and 'gain-of-function' mechanisms. Among the latter, covalent modifications specifically recruit a diverse array of modules, including the SH2 domain, 14-3-3, WW domain, Polo box, BRCT repeat, bromodomain, chromodomain, Tudor domain and motifs binding to ubiquitin and other protein modifiers. Such recruitments are often modulated by modifications occurred at neighboring and distant sites. Multisite modification thus coordinates intermolecular and intramolecular signaling for the qualitative and quantitative control of protein function in vivo.
282 citations
TL;DR: It is shown that binding of the bromodomain of TIP5, the large subunit of NoRC, to acetylated nucleosomes is a prerequisite for NoRC function and that the PHD finger/bromidomain represents an autonomous unit that binds to acH4K16 and coordinates the chain of events that establish the repressed state of rDNA.
151 citations
TL;DR: A transcription factor, CECR2, which is involved in neurulation and chromatin remodeling, and the presence of this protein as a component of a novel heterodimeric complex termed C ECR2-containing remodeling factor (CERF), which is capable of remodeling chromatin in vitro and displays an ATP hydrolyzing activity that is stimulated by nucleosomes.
Abstract: Chromatin remodeling complexes play critical roles in development. Here we describe a transcription factor, CECR2, which is involved in neurulation and chromatin remodeling. CECR2 shows complex alternative splicing, but all variants contain DDT and bromodomain motifs. A mutant mouse line was generated from an embryonic stem cell line containing a genetrap within Cecr2. Reporter gene expression demonstrated Cecr2 expression to be predominantly neural in the embryo. Mice homozygous for the Cecr2 genetrap-induced mutation show a high penetrance of the neural tube defect exencephaly, the human equivalent of anencephaly, in a strain-dependent fashion. Biochemical isolation of CECR2 revealed the presence of this protein as a component of a novel heterodimeric complex termed CECR2-containing remodeling factor (CERF). CERF comprises CECR2 and the ATP-dependent chromatin remodeler SNF2L, a mammalian ISWI ortholog expressed predominantly in the central nervous system. CERF is capable of remodeling chromatin in vitro and displays an ATP hydrolyzing activity that is stimulated by nucleosomes. Together, these data identify a novel chromatin remodeling complex with a critical role in neurulation.
149 citations
TL;DR: A novel class of N1-aryl-propane-1,3-diamine compounds are developed using a structure-based approach that selectively inhibit the activity of the bromodomain of the human transcriptional co-activator PCAF, of which association with the HIV trans-activators Tat is essential for transcription and replication of the integrated HIV provirus.
Abstract: Development of drug resistance from mutations in the targeted viral proteins leads to continuation of viral production by chronically infected cells, contributing to HIV-mediated immune dysfunction. Targeting a host cell protein essential for viral reproduction, rather than a viral protein, may minimize the viral drug resistance problem as observed with HIV protease inhibitors. We report here the development of a novel class of N1-aryl-propane-1,3-diamine compounds using a structure-based approach that selectively inhibit the activity of the bromodomain of the human transcriptional co-activator PCAF, of which association with the HIV trans-activator Tat is essential for transcription and replication of the integrated HIV provirus.
146 citations
TL;DR: P phenotypic analysis suggests that lysine 56 is critical for histone function and that it modulates formamide resistance, ultraviolet radiation sensitivity, and sensitivity to hydroxyurea, and reverse genetic analysis indicates that none of the known histone acetyltransferases is solely responsible for H3-K56 acetylation in Saccharomyces cerevisiae.
128 citations
TL;DR: The E2 protein modulates the chromatin association of Brd4 during both interphase and mitosis, demonstrating that the segregation of papillomavirus genomes is not simply due to the passive hitchhiking of the E2/genome complex with a convenient cellular chromosomal protein.
Abstract: The bovine papillomavirus E2 protein maintains and segregates the viral extrachromosomal genomes by tethering them to cellular mitotic chromosomes. E2 interacts with a cellular bromodomain protein, Brd4, to mediate the segregation of viral genomes into daughter cells. Brd4 binds acetylated histones and has been observed to diffusely coat mitotic chromosomes in several cell types. In this study, we show that in mitotic C127 cells, Brd4 diffusely coated the condensed chromosomes. However, in the presence of the E2 protein, E2 and Brd4 colocalized in punctate dots that were randomly distributed over the chromosomes. A similar pattern of E2 and Brd4 colocalization on mitotic chromosomes was observed in CV-1 cells, whereas only a faint chromosomal coating of Brd4 was detected in the absence of the E2 protein. Therefore, the viral E2 protein relocalizes and/or stabilizes the association of Brd4 with chromosomes in mitotic cells. The colocalization of E2 and Brd4 was also observed in interphase cells, indicating that this protein-protein interaction persists throughout the cell cycle. The interaction of E2 with Brd4 greatly stabilized the association of Brd4 with interphase chromatin. In both mitotic and interphase cells, this stabilization required a transcriptionally competent transactivation domain, but not the DNA binding function of the E2 protein. Thus, the E2 protein modulates the chromatin association of Brd4 during both interphase and mitosis. This study demonstrates that the segregation of papillomavirus genomes is not simply due to the passive hitchhiking of the E2/genome complex with a convenient cellular chromosomal protein.
TL;DR: DGcn5 is established as a major histone H3 acetylase in Drosophila which plays a key role in the control of specific morphogenetic cascades during developmental transitions, and in vivo complementation experiments revealed that dGcn 5 integrates specific functions in addition to chromosome binding and acetylation.
Abstract: Although it has been well established that histone acetyltransferases (HATs) are involved in the modulation of chromatin structure and gene transcription, there is only little information on their developmental role in higher organisms. Gcn5 was the first transcription factor with HAT activity identified in eukaryotes. Here we report the isolation and characterization of Drosophila melanogaster dGcn5 mutants. Null dGcn5 alleles block the onset of both oogenesis and metamorphosis, while hypomorphic dGcn5 alleles impair the formation of adult appendages and cuticle. Strikingly, the dramatic loss of acetylation of the K9 and K14 lysine residues of histone H3 in dGcn5 mutants has no noticeable effect on larval tissues. In contrast, strong cell proliferation defects in imaginal tissues are observed. In vivo complementation experiments revealed that dGcn5 integrates specific functions in addition to chromosome binding and acetylation. Surprisingly, a dGcn5 variant protein with a deletion of the bromodomain, which has been shown to recognize acetylated histones, appears to be fully functional. Our results establish dGcn5 as a major histone H3 acetylase in Drosophila which plays a key role in the control of specific morphogenetic cascades during developmental transitions.
TL;DR: Brd4+/- cells were impaired in their ability to recover from nocodazole-induced mitotic arrest: a large fraction of +/- cells failed to reach anaphases after drug withdrawal, and those that entered anaphase showed an increased frequency of abnormal chromosomal segregation.
Abstract: The mammalian bromodomain protein Brd4 interacts with mitotic chromosomes by binding to acetylated histone H3 and H4 and is thought to play a role in epigenetic memory. Mitotic cells are susceptible to antimicrotubule drugs. These drugs activate multiple response pathways and arrest cells at mitosis. We found that Brd4 was rapidly released from chromosomes upon treatment with antimicrotubule drugs, including the reversible agent nocodazole. Yet, when nocodazole was withdrawn, Brd4 was reloaded onto chromosomes, and cells proceeded to complete cell division. However, cells in which a Brd4 allele was disrupted (Brd4+/-), and expressing only half of the normal Brd4 levels, were defective in reloading Brd4 onto chromosomes. Consequently, Brd4+/- cells were impaired in their ability to recover from nocodazole-induced mitotic arrest: a large fraction of +/- cells failed to reach anaphase after drug withdrawal, and those that entered anaphase showed an increased frequency of abnormal chromosomal segregation. The reloading defect observed in Brd4+/- cells coincided with selective hypoacetylation of lysine residues on H3 and H4. The histone deacetylase inhibitor trichostatin A increased global histone acetylation and perturbed nocodazole-induced Brd4 unloading. Brd4 plays an integral part in a cellular response to drug-induced mitotic stress by preserving a properly acetylated chromatin status.
TL;DR: Epistasis analysis suggests that YTA7 and the HMR-tRNA function independently to restrict the spread of silencing, while RSC2 may function through the tRNA element, suggesting that multiple bromodomain proteins are involved in restricting the propagation of heterochromatin at HMR.
Abstract: The transfer RNA gene downstream from the HMR locus in S. cerevisiae functions as part of a boundary (barrier) element that restricts the spread of heterochromatic gene silencing into the downstream region of chromosome III. A genetic screen for identifying additional genes that, when mutated, allow inappropriate spreading of silencing from HMR through the tRNA gene was performed. YTA7, a gene containing bromodomain and ATPase homologies, was identified multiple times. Previously, others had shown that the bromodomain protein Bdf1p functions to restrict silencing at yeast euchromatin-heterochromatin boundaries; therefore we deleted nonessential bromodomain-containing genes to test their effects on heterochromatin spreading. Deletion of RSC2, coding for a component of the RSC chromatin-remodeling complex, resulted in a significant spread of silencing at HMR. Since the bromodomain of YTA7 lacks a key tyrosine residue shown to be important for acetyllysine binding in other bromodomains, we confirmed that a GST-Yta7p bromodomain fusion was capable of binding to histones in vitro. Epistasis analysis suggests that YTA7 and the HMR-tRNA function independently to restrict the spread of silencing, while RSC2 may function through the tRNA element. Our results suggest that multiple bromodomain proteins are involved in restricting the propagation of heterochromatin at HMR.
TL;DR: It is shown that GENERAL TRANSCRIPTION FACTOR GROUP E6 (GTE6) regulates differences in leaf patterning between juvenile and mature leaves in Arabidopsis, ensuring the continual production of mature leaves following juvenile-adult transition, thereby maintaining the identity of the mature vegetative phase.
Abstract: The transition from the juvenile to the mature phase during vegetative development in plants is characterized by changes in leaf shape. We show that GENERAL TRANSCRIPTION FACTOR GROUP E6 (GTE6) regulates differences in leaf patterning between juvenile and mature leaves in Arabidopsis. GTE6 encodes a novel small bromodomain-containing protein unique to plants. Mutations in GTE6 disrupt the formation of elliptical leaf laminae in mature leaves, whereas overexpression of GTE6 resulted in elongated juvenile leaves. GTE6 positively regulates the expression of ASYMMETRIC LEAVES1 (AS1), which encodes a myb-domain protein that controls proximodistal patterning of leaves. Using chromatin immunoprecipitation (ChIP) assays, we show that GTE6 is associated with the promoter and the start of the transcribed region of AS1 and up-regulates expression of AS1 through acetylation of histones H3 and H4. Genetic studies demonstrated that AS1 is epistatic to GTE6, indicating that GTE6 regulates AS1 during leaf morphogenesis. Chromatin remodeling at AS1 is a key regulatory mechanism in leaf development, which ensures the continual production of mature leaves following juvenile-adult transition, thereby maintaining the identity of the mature vegetative phase.
01 Jan 2005
TL;DR: This paper presents a meta-modelling study of the structure and molecular Interactions of the Bromodomain in yeast two-hybrid Protein-Protein Interaction Networks and discusses the role of Mass Spectrometry in studying protein-P Protein Interaction.
Abstract: Introduction: Proteomics and Protein-Protein Interactions: Biology, Chemistry, Bioinformatics, and Drug Design.- Yeast Two-Hybrid Protein-Protein Interaction Networks.- The Use of Mass Spectrometry in Studying Protein-Protein Interaction.- Molecular Recognition in the Immune System.- Computational Methods for Predicting Protein-Protein Interactions.- Protein-Protein Docking Methods.- Thermochemistry of Binary and Ternary Protein Interactions Measured by Titration Calorimetry: Complex Formation of CD4, HIV gp120, and Anti-gp120.- Protein-Protein Recognition in Phosphotyrosine-Mediated Intracellular Signaling.- Competitive Binding of Proline-Rich Sequences by SH3, WW, and Other Functionally Related Protein Domains.- The Structure and Molecular Interactions of the Bromodomain.- SMART Drug Design: Novel Phosphopeptide and ATP Mimetic-Based Small Molecule Inhibitors of the Oncogenic Protein Kinase pp60src (Src).- Disrupting Protein-Protein Interaction: Therapeutic Tools Against Brain Damage.- A Thermodynamic Guide to Affinity Optimization of Drug Candidates.
TL;DR: It is suggested that the coordination between the amino acid sequence RHRK20VLRDN and the SET domain of SET8 determines the substrate specificity and multiplicity of methylation of lysine 20 of H4.
TL;DR: The interaction between CtBP and CBP is functionally important and leads to impairment of histone H3 acetylation by CBP at specific lysine residues (Lys9, Lys14, and Lys18) in a dose-dependent and NADH-dependent manner.
TL;DR: The experimental methods that have allowed the detection and functional analysis of acetylated forms of NF-κB are described, including anti-acetylated lysine antibodies for immunoblotting and anti-RelA antibodies that selectively react with site-specific acetylation forms of RelA.
TL;DR: Structural-based sequence analysis reveals several features that may be involved in mediating protein-protein interactions in chicken polybromo (BAH1), including a HMG box and AT hook.
Abstract: The BAH domain (bromo-associated homology domain) was first identified from a repeated motif found in the nuclear protein polybromo--a large (187 kDa) modular protein comprising six bromodomains, two BAH domains and an HMG box. To date, the BAH domain has no ascribed function, although it is found in a wide range of proteins that contain additional domains involved in either transcriptional regulation (e.g. SET, PHD and bromodomain) and/or DNA binding (HMG box and AT hook). The molecular function of polybromo itself also remains unclear, but it has been identified as a key component of an SWI/SNF (switching/sucrose non-fermenting)-related, ATP-dependent chromatin-remodelling complex PBAF (polybromo, BRG1-associated factors; also known as SWI/SNF-B or SWI/SNFbeta). We present in this paper the crystal structure of the proximal BAH domain from chicken polybromo (BAH1), at a resolution of 1.6 A (1 A=0.1 nm). Structure-based sequence analysis reveals several features that may be involved in mediating protein-protein interactions.
TL;DR: The findings suggest that SET domain proteins such as Gö1‐SET may restructure archaeal chromatin that is composed of MC1–DNA complexes, and that modulation of chromatin structure by lysine methylation may have arisen before the divergence of the Archaeal and eukaryotic lineages.
TL;DR: The physical interfaces of the p53 protein with cellular proteins are examined to show that amino acids Trp, Met and Phe are critical for protein-protein interactions in general and may assist in elucidating the p 53 interactions when structural data are not available.
Abstract: Dynamic molecular interaction networks underlie biological phenomena. Among the many genes which are involved, p53 plays a central role in networks controlling cellular life and death. It not only operates as a tumor suppressor, but also helps regulate hundreds of genes in response to various types of stress. To accomplish these functions as a guardian of the genome, p53 interacts extensively with both nucleic acids and proteins. This paper examines the physical interfaces of the p53 protein with cellular proteins. Previously, in the analysis of the structures of protein–protein complexes, we have observed that amino acids Trp, Met and Phe are important for protein–protein interactions in general. Here we show that these residues are critical for the many functions of p53. Several clusters of the Trp/Met/Phe residues are involved in the p53 protein–protein interactions. Phe19/Trp23 in the TA1 region extensively binds to the transcriptional factors and the MDM2 protein. Trp53/Phe54 in the TA2 region is crucial for transactivation and DNA replication. Met243 in the core domain interacts with 53BP1, 53BP2 and Rad 51 proteins. Met384/Phe385 in the C-terminal region interacts with the S100B protein and the Bromodomain of the CBP protein. Thus, these residues may assist in elucidating the p53 interactions when structural data are not available.
TL;DR: Fluorescence resonance energy transfer experiments performed in this work demonstrate that P/CAF proteins in which tyrosines are mutated into hydrophilic residues neither bind to Tat inside the cells nor mediate Tat transactivation.
Abstract: Structural and functional studies indicate that, through its bromodomain, the cellular acetyltransferase P/CAF binds the acetylated Tat protein of human immunodeficiency virus type 1 (HIV-1) and promotes transcriptional activation of the integrated provirus. Based on the NMR structure of P/CAF complexed with an acetylated Tat peptide, here we use molecular dynamics simulations to construct a model describing the interaction between full length Tat and the P/CAF bromodomain. Our calculations show that the protein-protein interface involves hydrophobic interactions between the P/CAF ZA loop and the Tat core domain. In particular, tyrosines 760 and 761 of P/CAF, two residues that are highly conserved in most known bromodomains, play an essential role for the binding. Fluorescence resonance energy transfer (FRET) experiments performed in this work demonstrate that P/CAF proteins in which these tyrosines are mutated into hydrophilic residues neither bind to Tat inside the cells nor mediate Tat transactivation. The combination of theoretical and in vivo studies provides new insights into the specificity of bromodomain recognition.
TL;DR: It is suggested that this molecule plays a role in allowing cells to enter the proliferative phase of the angiogenic process.
Abstract: By screening differentially expressed genes in mouse embryonic stem (ES) cells by subtractive hybridization, we identified three conserved but uncharacterized genes encoding bromodomain containing 3 (BRD3), protein lysine methyltransferase (PLM), and kelch domain containing 2 (KLHDC2), which were downregulated during endothelial differentiation. An RNA blot study showed that these genes were markedly expressed in undifferentiated ES cells, whereas the expression was reduced upon endothelial differentiation; a study of mouse endothelium showed a significant reduction in the expression of BRD3. A study of human BRD3, located on chromosome 9 at q34, a region susceptible to genomic rearrangement, showed an altered expression in 4 of 12 patients with bladder cancer, compared with adjacent noncancerous tissues. Taken together with the result of siRNA inhibition showing the positive regulation of cell proliferation by BRD3, it is suggested that this molecule plays a role in allowing cells to enter the proliferat...
TL;DR: This work suggests an approach for the artificial control of transcriptional activation through the use of highly amphiphilic small molecules that would mimic the action of acetylated lysines and holds promise for advances in cancer etiology and treatment.
Abstract: Post-translational acetylation of lysines of the histone N-terminal tails is known to induce transcriptional activation, and thus plays a major role in gene regulation. A mechanism for this effect is suggested by our recent finding that the initial 'solvation' network, which is formed around the purines of base pairs immediately following their opening, has the tendency to be preserved. The experiments involved studying the solvation of nucleosides in water-alcohol mixtures; these systems model the hydrophobic/hydrophilic effects that participate in the interaction between histone-tail amino acid residues and nucleosomal DNA base pairs following their opening by the action of DNA-binding proteins in conjunction with remodeling complexes. A highly amphiphilic molecular environment, which has a four-carbon aliphatic chain and hydrogen bond accepting and donating capabilities, was found to promote this phenomenon. Acetylated lysines, unlike lysines, possess these properties and thus constitute such a molecular environment. Opened base pairs are maintained by direct interactions of their purines with acetylated lysines that are selectively recognized by the bromodomains of the recruited remodeling complexes. This maintenance is in accord with the reported large enhancements of i) transcription factor binding to nucleosomal DNA and (ii) the degree of DNA flexibility, which are associated with histone-tail acetylation. This mechanism suggests a way to possibly establish an orderly sequence of transcriptional events despite the reported prevailing stochasticity. It also suggests an approach for the artificial control of transcriptional activation through the use of highly amphiphilic small molecules that would mimic the action of acetylated lysines; in view of the known association of aberrant transcription with cancer, this approach holds promise for advances in cancer etiology and treatment and represents an alternative to the approach that currently uses histone deacetylase inhibitors (some of which are in clinical trials).
Dissertation•
01 Jan 2005
TL;DR: Functional similarities and differences of KSHV LANA-1 and homologous orf73 proteins of the related γ2-herpesviruses rhesus rhadinovirus (RRV), herpesvirus saimiri (HVS) and MHV-68 are defined and a conserved region in the C-terminal regions of orf 73 proteins are identified to be crucial for BRD2 and BRD4 binding.
Abstract: Kaposi’s sarcoma associated
herpesvirus (KSHV) is a human pathogen of major importance mainly in the immunocompromised.
The latency-associated nuclear antigen 1 (LANA-1) of KSHV, encoded by the
open reading frame 73 (orf73), fulfils multiple functions vital to viral
latency. However, the majority of data concerning LANA-1 function are
generated in vitro. Since for
example murine γ-herpesvirus 68 (MHV-68) infection of its natural mouse
host could potentially provide a suitable animal model to study γ2-herpesviral
orf73 functional biology in vivo, we
were seeking to define functional similarities and differences of KSHV LANA-1
and homologous orf73 proteins of the related γ2-herpesviruses
rhesus rhadinovirus (RRV), herpesvirus saimiri (HVS) and MHV-68.
We found several KSHV LANA-1
functions that are also provided by the MHV-68 orf73 protein, such as
transcriptional activation of the cell cycle dependent promoters of cyclins E
and D2, transcriptional repression of a viral promoter/enhancer element,
dimerisation/oligomerisation, chromatin association, the replication of
terminal repeat containing plasmids and the interaction with cellular
proteins such as the retinoblastoma tumour suppressor protein. Hence, the
MHV-68 orf73 protein could potentially provide a valuable model system to
investigate orf73 protein function in
vivo in mice.
Additionally, based on the earlier
observation by our group, that KSHV LANA-1 interacts with BRD2/RING3, we
demonstrated KSHV LANA-1 and the orf73 homologs to interact with the celluar
bromodomain-containing proteins BRD2/RING3 and BRD4/HUNK. Bromodomains are
chromatin-targeting modules and BRD2 and BRD4 are known to interact with
chromatin and to modulate transcription and cell cycle events. We showed the
C-terminal regions of BRD2 and BRD4 to be responsible for binding to orf73
proteins. Further, we identified a conserved region in the C-terminal regions
of orf73 proteins to be crucial for BRD2 and BRD4 binding.
Orf73 proteins of MHV-68 and RRV
increased the expression levels of BRD2 and BRD4 in cotransfected cells.
Further, we showed that activation of the cell cycle- dependent cyclinE
promoter by BRD4 was negatively regulated by the orf73 proteins of KSHV and
RRV.
Using dominant negative BRD4 mutants
and an siRNA approach, we provide initial data indicating a role of BRD4 in
the KSHV LANA-1 mediated replication of a terminal repeat containing plasmid.
Journal Article•
TL;DR: EMotif analysis revealed that BRD7 protein contains a conserved bromodomain and several important phosphorylation sites, and multiple sequence alignment program showed high ratio identity between BRD 7 protein, protein Celtix-1 and musculus bromidomain-containing protein BP75.
Abstract: Bromodomain is an evolutionally conserved domain and is identified in proteins strongly implicated insignal-dependent gene transcription regulation BRD7, a novel bromodomain gene, has been cloned by cDNARDA (cDNA Representational Difference Analysis) in 1999 The GenBank accession number is AF152604 orAF152605 eMotif analysis revealed that BRD7 protein contains a conserved bromodomain and several importantphosphorylation sites Multiple sequence alignment program showed high ratio identity between BRD7 protein,protein Celtix-1 and musculus bromodomain-containing protein BP75 Over expression of BRD7 inNasopharyngeal carcinoma (NPC) cells can inhibit cell proliferation and cell cycle progression from G1 to S phase,and can partly inhibit the aberrant growth of NPC cells In order to further address the signal pathway and thepossible functions of BRD7 gene, function analysis of BRD7 gene was performed through three different cellularphysiology levels including up- and down-stream, interplay issues of BRD7 gene
11 May 2005
01 Jan 2005
TL;DR: Structural analyses of bromodomains in complex with acetyl-lysine-containing biological ligands provide insights into the molecular basis of differences in ligand selectivity of the bromidomain family, and reinforce the concept that functional diversity of a conserved protein structure is achieved by evolutionary changes of amino acid sequences in the ligand binding site.
Abstract: The bromodomain is a structurally conserved protein module that is present in a large number of chromatin-associated proteins and in many nuclear histone acetyltransferases. The bromodomain functions as an acetyl-lysine binding domain and has recently been shown to play an important role in regulating protein-protein interactions in chromatin-mediated cellular gene transcription as well as in viral transcriptional activation. Recent structural analyses of bromodomains in complex with acetyl-lysine-containing biological ligands provide insights into the molecular basis of differences in ligand selectivity of the bromodomain family, and reinforce the concept that functional diversity of a conserved protein structure is achieved by evolutionary changes of amino acid sequences in the ligand binding site.