Wdr82 is a C-terminal domain-binding protein that recruits the Setd1A Histone H3-Lys4 methyltransferase complex to transcription start sites of transcribed human genes.
Jeong Heon Lee,David G. Skalnik +1 more
Reads0
Chats0
TLDR
The results suggest a model for how the mammalian RNAP II machinery is linked with histone H3-Lys4 histone methyltransferase complexes at transcriptionally active genes.Abstract:
Histone H3-Lys4 trimethylation is associated with the transcription start site of transcribed genes, but the molecular mechanisms that control this distribution in mammals are unclear. The human Setd1A histone H3-Lys4 methyltransferase complex was found to physically associate with the RNA polymerase II large subunit. The Wdr82 component of the Setd1A complex interacts with the RNA recognition motif of Setd1A and additionally binds to the Ser5-phosphorylated C-terminal domain of RNA polymerase II, which is involved in initiation of transcription, but does not bind to an unphosphorylated or Ser2-phosphorylated C-terminal domain. Chromatin immunoprecipitation analysis revealed that Setd1A is localized near the transcription start site of expressed genes. Small interfering RNA-mediated depletion of Wdr82 leads to decreased Setd1A expression and occupancy at transcription start sites and reduced histone H3-Lys4 trimethylation at these sites. However, neither RNA polymerase II (RNAP II) occupancy nor target gene expression levels are altered following Wdr82 depletion. Hence, Wdr82 is required for the targeting of Setd1A-mediated histone H3-Lys4 trimethylation near transcription start sites via tethering to RNA polymerase II, an event that is a consequence of transcription initiation. These results suggest a model for how the mammalian RNAP II machinery is linked with histone H3-Lys4 histone methyltransferase complexes at transcriptionally active genes.read more
Citations
More filters
Journal ArticleDOI
Transcriptional regulation of macrophage polarization: enabling diversity with identity.
Toby Lawrence,Gioacchino Natoli +1 more
TL;DR: This Review summarizes the current knowledge of transcriptional and chromatin-mediated control of macrophage polarization in physiology and disease and describes a complex interplay between microenvironmental signals and a hardwired differentiation programme that determines Macrophage identity.
Journal ArticleDOI
Modification of Enhancer Chromatin: What, How, and Why?
Eliezer Calo,Joanna Wysocka +1 more
TL;DR: An overview of enhancer-associated modifications of histones and DNA is given and enzymatic activities involved in their dynamic deposition and removal are discussed and potential downstream effectors of these marks are described.
Journal ArticleDOI
The let-7 family of microRNAs.
Sarah F. Roush,Frank J. Slack +1 more
TL;DR: The let-7-family conservation and the recent advances in understanding how let- 7-expression is regulated at the transcriptional and post-transcriptional levels across species are reviewed.
Journal ArticleDOI
The COMPASS family of histone H3K4 methylases: mechanisms of regulation in development and disease pathogenesis.
TL;DR: The process of histone H2B monoubiquitination-dependent and -independent hist one H3K4 methylation as a mark of active transcription, enhancer signatures, and developmentally poised genes is discussed and recent findings in this regard are examined.
Journal ArticleDOI
Writing, erasing and reading histone lysine methylations
TL;DR: A more detailed understanding of histone lysine methylation is necessary for elucidating complex biological processes and, ultimately, for developing and improving disease treatments.
References
More filters
Journal ArticleDOI
A Bivalent Chromatin Structure Marks Key Developmental Genes in Embryonic Stem Cells
Bradley E. Bernstein,Tarjei S. Mikkelsen,Tarjei S. Mikkelsen,Xiaohui Xie,Michael Kamal,Dana J. Huebert,James Cuff,Ben Fry,Alexander Meissner,Marius Wernig,Kathrin Plath,Rudolf Jaenisch,Alexandre Wagschal,Robert Feil,Stuart L. Schreiber,Stuart L. Schreiber,Eric S. Lander,Eric S. Lander +17 more
TL;DR: It is proposed that bivalent domains silence developmental genes in ES cells while keeping them poised for activation, highlighting the importance of DNA sequence in defining the initial epigenetic landscape and suggesting a novel chromatin-based mechanism for maintaining pluripotency.
Journal ArticleDOI
A Chromatin Landmark and Transcription Initiation at Most Promoters in Human Cells
TL;DR: The results of a genome-wide analysis of human cells suggest that most protein-coding genes, including most genes thought to be transcriptionally inactive, experience transcription initiation, and that transcription initiation at most genes is a general phenomenon in human cells.
Journal ArticleDOI
Genomic Maps and Comparative Analysis of Histone Modifications in Human and Mouse
Bradley E. Bernstein,Bradley E. Bernstein,Bradley E. Bernstein,Michael Kamal,Kerstin Lindblad-Toh,Stefan Bekiranov,Dione K. Bailey,Dana J. Huebert,Dana J. Huebert,Scott McMahon,Scott McMahon,Elinor K. Karlsson,Edward J. Kulbokas,Thomas R. Gingeras,Stuart L. Schreiber,Stuart L. Schreiber,Eric S. Lander,Eric S. Lander +17 more
TL;DR: Methylation patterns at orthologous loci are strongly conserved between human and mouse even though many methylated sites do not show sequence conservation notably higher than background, which suggests that the DNA elements that direct the methylation represent only a small fraction of the region or lie at some distance from the site.
Journal ArticleDOI
Genome-wide map of nucleosome acetylation and methylation in yeast.
Dmitry K. Pokholok,Christopher T. Harbison,Stuart S. Levine,Megan F. Cole,Nancy M. Hannett,Tong Ihn Lee,George W. Bell,Kimberly Walker,P. Alex Rolfe,Elizabeth Herbolsheimer,Julia Zeitlinger,Fran Lewitter,David K. Gifford,Richard A. Young +13 more
TL;DR: These maps take into account changes in nucleosome occupancy at actively transcribed genes and, in doing so, revise previous assessments of the modifications associated with gene expression, providing the foundation for further understanding the roles of chromatin in gene expression and genome maintenance.
Journal ArticleDOI
Targeted Recruitment of Set1 Histone Methylase by Elongating Pol II Provides a Localized Mark and Memory of Recent Transcriptional Activity
TL;DR: Hypermethylated H3-K4 within the mRNA coding region persists for considerable time after transcriptional inactivation and Set1 dissociation from the chromatin, indicating that H3/K4 hypermethylation provides a molecular memory of recent transcriptional activity.