Author
John W. Tamkun
Other affiliations: University of Colorado Boulder, Stanford University, Massachusetts Institute of Technology
Bio: John W. Tamkun is an academic researcher from University of California, Santa Cruz. The author has contributed to research in topics: Chromatin & Chromatin remodeling. The author has an hindex of 38, co-authored 51 publications receiving 10591 citations. Previous affiliations of John W. Tamkun include University of Colorado Boulder & Stanford University.
Topics: Chromatin, Chromatin remodeling, Homeotic gene, Histone, Gene
Papers published on a yearly basis
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TL;DR: The brahma (brm) gene encodes a 1638 residue protein that is similar to SNF2/SWI2, a protein involved in transcriptional activation in yeast, suggesting possible models for the role of brm in the transcriptionalactivation of homeotic genes.
951 citations
928 citations
TL;DR: The name integrin is proposed for this protein complex to denote its role as an integral membrane complex involved in the transmembrane association between the extracellular matrix and the cytoskeleton.
851 citations
TL;DR: The results show that the SWI2 family DNA-dependent ATPase domain has functional con-servation between yeast and humans and suggest that a SWI/SNF protein complex is required for the activation of selective mammalian genes.
Abstract: SEQUENCE-SPECIFIC DNA binding activators of gene transcription may be assisted by SWI2(SNF2)1,2, which contains a DNA-depen-dent ATPase domain3. We have isolated a human complementary DNA encoding a 205K nuclear protein, BRG1, that contains extensive homology to SWI2 and Drosophila brahma4,5. We report here that a SWI2/BRG1 chimaera with the DNA-dependent ATPase domain replaced by corresponding human sequence restored normal mitotic growth and capacity for transcriptional activation to swi2& minus; yeast cells. Point mutation of the conserved ATP binding site lysine abolished this complementation. This mutation in SW12 exerted a dominant negative effect on transcription in yeast. A lysine to arginine substitution at the corresponding residue of BRG1 also generated a transcriptional dominant negative in human cells. BRG1 is exclusively nuclear and present in a high Mr complex of about 2 & times; 106. These results show that the SWI2 family DNA-dependent ATPase domain has functional con-servation between yeast and humans and suggest that a SWI/SNF protein complex is required for the activation of selective mammalian genes.
661 citations
TL;DR: There are at least three different fibronectin mRNAs in rat liver which differ in coding potential and are probably all encoded by a single gene, according to the sequence data and S1 nuclease mapping.
659 citations
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TL;DR: Together, the adhesion proteins and their receptors constitute a versatile recognition system providing cells with anchorage, traction for migration, and signals for polarity, position, differentiation, and possibly growth.
Abstract: Rapid progress has been made in the understanding of the molecular interactions that result in cell adhesion. Many adhesive proteins present in extracellular matrices and in the blood contain the tripeptide arginine-glycine-aspartic acid (RGD) as their cell recognition site. These proteins include fibronectin, vitronectin, osteopontin, collagens, thrombospondin, fibrinogen, and von Willebrand factor. The RGD sequences of each of the adhesive proteins are recognized by at least one member of a family of structurally related receptors, integrins, which are heterodimeric proteins with two membrane-spanning subunits. Some of these receptors bind to the RGD sequence of a single adhesion protein only, whereas others recognize groups of them. The conformation of the RGD sequence in the individual proteins may be critical to this recognition specificity. On the cytoplasmic side of the plasma membrane, the receptors connect the extracellular matrix to the cytoskeleton. More than ten proved or suspected RGD-containing adhesion-promoting proteins have already been identified, and the integrin family includes at least as many receptors recognizing these proteins. Together, the adhesion proteins and their receptors constitute a versatile recognition system providing cells with anchorage, traction for migration, and signals for polarity, position, differentiation, and possibly growth.
4,821 citations
TL;DR: This brief review of sequence data from embryogenesis, thrombosis, and lymphocyte help and killing is summarized and attempts to clarify the relationships among the members of this family of cell surface receptors.
4,229 citations
TL;DR: The purification and characterization of an EED-EZH2 complex, the human counterpart of the Drosophila ESC-E(Z) complex, is reported, and it is demonstrated that the complex specifically methylates nucleosomal histone H3 at lysine 27 (H3-K27).
Abstract: Polycomb group (PcG) proteins play important roles in maintaining the silent state of HOX genes. Recent studies have implicated histone methylation in long-term gene silencing. However, a connection between PcG-mediated gene silencing and histone methylation has not been established. Here we report the purification and characterization of an EED-EZH2 complex, the human counterpart of the Drosophila ESC-E(Z) complex. We demonstrate that the complex specifically methylates nucleosomal histone H3 at lysine 27 (H3-K27). Using chromatin immunoprecipitation assays, we show that H3-K27 methylation colocalizes with, and is dependent on, E(Z) binding at an Ultrabithorax (Ubx) Polycomb response element (PRE), and that this methylation correlates with Ubx repression. Methylation on H3-K27 facilitates binding of Polycomb (PC), a component of the PRC1 complex, to histone H3 amino-terminal tail. Thus, these studies establish a link between histone methylation and PcG-mediated gene silencing.
3,565 citations
TL;DR: The results reaffirm the thesis that miRNAs have an important role in establishing the complex spatial and temporal patterns of gene activity necessary for the orderly progression of development and suggest additional roles in the function of the mature organism.
Abstract: Background: The recent discoveries of microRNA (miRNA) genes and characterization of the first few target genes regulated by miRNAs in Caenorhabditis elegans and Drosophila melanogaster have set the stage for elucidation of a novel network of regulatory control. We present a computational method for wholegenome prediction of miRNA target genes. The method is validated using known examples. For each miRNA, target genes are selected on the basis of three properties: sequence complementarity using a position-weighted local alignment algorithm, free energies of RNA-RNA duplexes, and conservation of target sites in related genomes. Application to the D. melanogaster, Drosophila pseudoobscura and Anopheles gambiae genomes identifies several hundred target genes potentially regulated by one or more known miRNAs.
2,997 citations
TL;DR: This review summarizes recent studies that define structural domains for DNA binding and transcriptional activation functions in sequence-specific transcription factors in mammalian DNA binding transcription factors.
Abstract: The cloning of genes encoding mammalian DNA binding transcription factors for RNA polymerase II has provided the opportunity to analyze the structure and function of these proteins. This review summarizes recent studies that define structural domains for DNA binding and transcriptional activation functions in sequence-specific transcription factors. The mechanisms by which these factors may activate transcriptional initiation and by which they may be regulated to achieve differential gene expression are also discussed.
2,911 citations