Genome-wide mapping of HATs and HDACs reveals distinct functions in active and inactive genes

By Zhibin Wang, Chongzhi Zang, Kairong Cui, Dustin E. Schones, A. Barski, Weiqun Peng, Keji Zhao. Cell, 2009

1,342 citations recorded by the source corpus.

Histone acetyltransferases (HATs) and histone deacetylases (HDACs) function antagonistically to control histone acetylation states that are crucial to many cellular processes. We describe here genome-wide mapping experiments that reveal that both HATs (CBP, p300, PCAF, Tip60, MOF) and HDACs (HDAC1, HDAC2, HDAC3, HDAC6) on chromatin are positively correlated with gene expression and histone acetylation. We provide evidence that Tip60 and HDAC6 are targeted to transcribed regions of active genes by phosphorylated RNA Pol II. Our results indicate that MLL-mediated H3K4 methylation primes chromatin to facilitate histone acetylation. Our data suggest that the majority of HDACs in the human genome function to reset chromatin by removing acetylation in active genes; the dynamic cycle of acetylation and deacetylation by transient HAT/HDAC binding prevents Pol II from binding to the genes primed by H3K4 methylation and poises them for future activation.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/dc02bda15e416a6775a53bf0c87fce83e1b8d4c6

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Citations in the corpus

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Erasers of histone acetylation: the histone deacetylase enzymes. (2014, background): “However, in another genome-wide mapping study, HDACs were found bound to chromatin at active genes but not silent genes (Wang et al. 2009).”
The Language of Histone Crosstalk (2010, background): “Another example of trans-tail crosstalk was proposed by Wang et al. (2009).”
Mammalian SWI/SNF chromatin remodeling complexes and cancer: Mechanistic insights gained from human genomics (2015, background): “, unpublished data), whichmight reflect their opposition in much the same way the histone acetylases and deacetylase co-bind over the genome, reflecting their constant opposition and the highly labile nature of this histone modification (53).”
DEEP: a general computational framework for predicting enhancers (2014, methodology): “For CSI-ANN, all predictions were obtained based on the optimal model proposed by the authors, trained on CD4+T cell line data (32).”
Chemoproteomics profiling of HDAC inhibitors reveals selective targeting of HDAC complexes (2011, background): “HDAC6 has recently been implicated in chromatin regulatio”
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Feedback regulation of EGFR signalling: decision making by early and delayed loops (2011, background): “A putative, pre-emptive regulatory process to counteract this has been described in resting T cells: unlike active genes, the associated histones of which are constitutively acetylated by histone acetyltransferases (HATs), the promoters of a group of primed genes (for example, FOS related antigen 1 ”
Epigenetic modifications and human disease (2010, background): “Thus, most HDACs in the human genome function to reset chromatin by removing acetylation at active genes, whereas HATs, by contrast, are mainly linked to transcriptional activatio”
Human HDAC1 and HDAC2 function in the DNA-damage response to promote DNA non-homologous end-joining (2010, neutral): “Histone hypoacetylation is generally associated with transcriptionally silent chromatin, and H3K56Ac and H4K16Ac are histone marks that are associated with transcriptional activatio”
Quantitative interaction proteomics and genome-wide profiling of epigenetic histone marks and their readers. (2010, background): “These data may be explained by invoking a mechanism of cyclical recruitment of ‘‘writers’’ and ‘‘erasers’’ to sites of active transcription (Wang et al., 2009c).”
Histone modification levels are predictive for gene expression (2010, background): “Finally, gene expression levels of another cell type were accurately predicted using a model trained on the CD 4 þ T-cells, suggesting that the relationship be-tween histone modifications and gene expression is a general one.”