Readers of histone modifications

Yun, Miyong; Wu, Jun; Workman, Jerry L.; Li, Bing

doi:10.1038/cr.2011.42

Cited by 506 publications

(414 citation statements)

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“…Preliminary assessments suggested that the yTAF1/7 pocket 2 is a likely candidate for recognition of the H3K27me3 repressive mark; the pocket 2 wall aromatic residues could create a hydrophobic aromatic cage, favorable for accommodation of the hydrophobic trimethylated lysine side chain (26), whereas the negatively charged pocket floor could neutralize positive charges on the H3K27me3 peptide. We tested this possibility using mutational analysis combined with peptide affinity studies.…”

Section: Resultsmentioning

confidence: 99%

Structural and functional insight into TAF1–TAF7, a subcomplex of transcription factor II D

Bhattacharya

Lou

Hwang

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Transcription factor II D (TFIID) is a multiprotein complex that nucleates formation of the basal transcription machinery. TATA binding protein-associated factors 1 and 7 (TAF1 and TAF7), two subunits of TFIID, are integral to the regulation of eukaryotic transcription initiation and play key roles in preinitiation complex (PIC) assembly. Current models suggest that TAF7 acts as a dissociable inhibitor of TAF1 histone acetyltransferase activity and that this event ensures appropriate assembly of the RNA polymerase IImediated PIC before transcriptional initiation. Here, we report the 3D structure of a complex of yeast TAF1 with TAF7 at 2.9 Å resolution. The structure displays novel architecture and is characterized by a large predominantly hydrophobic heterodimer interface and extensive cofolding of TAF subunits. There are no obvious similarities between TAF1 and known histone acetyltransferases. Instead, the surface of the TAF1-TAF7 complex contains two prominent conserved surface pockets, one of which binds selectively to an inhibitory trimethylated histone H3 mark on Lys27 in a manner that is also regulated by phosphorylation at the neighboring H3 serine. Our findings could point toward novel roles for the TAF1-TAF7 complex in regulation of PIC assembly via reading epigenetic histone marks.initiation complex | protein structure | protein-protein interaction | X-ray crystallography T he general transcription factor II D (TFIID) plays a central role in recognition of the core promoter element and mediates accurate transcription initiation by RNA Polymerase (Pol) II for a large class of genes. TFIID nucleates the formation of the preinitiation complex (PIC) at the transcriptional start site by recruiting other general transcription factors (TFII-A, -B, -E, -F, and -H), along with RNA Pol II. TFIID is assembled in a stepwise manner, with a symmetric TFIID core complex recruited first, followed by further recruitment of additional TATA binding protein (TBP)-associated factors (TAFs) to form the complete asymmetric holo-TFIID complex (1). This megadalton-sized multiprotein assembly, comprised of TBP and 13 evolutionary conserved TAFs (2), is organized into a trilobed structure (3) and undergoes striking rearrangements upon binding to TFIIA and DNA (4). TAF subunits serve multiple functions within the TFIID holocomplex. In addition to TBP, TAF1, TAF2, TAF6, and TAF9 are also involved in recognition of DNA initiator and promoter elements. Moreover, TFIID can behave as an epigenetic effector, capable of recognizing posttranslational histone modifications associated with activated transcription. Eukaryotic TAF1 contains a double bromodomain that recognizes acetylated histones, and TAF3 contains a plant homeo domain (PHD) that binds to histone H3 methylated at lysine 4 (5, 6). In addition to roles in basal transcription, TFIID is also associated with diseases. Overexpression of TAF1, which acts as a specific coactivator of androgen receptor, is related to the progression of human prostate cancer (7). Additionally, altera...

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Section: Resultsmentioning

confidence: 99%

Structural and functional insight into TAF1–TAF7, a subcomplex of transcription factor II D

Bhattacharya

Lou

Hwang

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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“…Some modifications of histones include acetylation, methylation, and ubiquitylation. These modifications can alter the structural properties of nucleosomes and serve as specific effectors for the recruitment of proteins that further modify the chromatin template and regulate transcription (1).…”

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confidence: 99%

Small region of Rtf1 protein can substitute for complete Paf1 complex in facilitating global histone H2B ubiquitylation in yeast

Piro

Mayekar

Warner

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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Histone modifications regulate transcription by RNA polymerase II and maintain a balance between active and repressed chromatin states. The conserved Paf1 complex (Paf1C) promotes specific histone modifications during transcription elongation, but the mechanisms by which it facilitates these marks are undefined. We previously identified a 90-amino acid region within the Rtf1 subunit of Paf1C that is necessary for Paf1C-dependent histone modifications in Saccharomyces cerevisiae. Here we show that this histone modification domain (HMD), when expressed as the only source of Rtf1, can promote H3 K4 and K79 methylation and H2B K123 ubiquitylation in yeast. The HMD can restore histone modifications in rtf1Δ cells whether or not it is directed to DNA by a fusion to a DNA binding domain. The HMD can facilitate histone modifications independently of other Paf1C subunits and does not bypass the requirement for Rad6-Bre1. The isolated HMD localizes to chromatin, and this interaction requires residues important for histone modification. When expressed outside the context of fulllength Rtf1, the HMD associates with and causes Paf1C-dependent histone modifications to appear at transcriptionally inactive loci, suggesting that its function has become deregulated. Finally, the Rtf1 HMDs from other species can function in yeast. Our findings suggest a direct and conserved role for Paf1C in coupling histone modifications to transcription elongation.transcription-coupled histone modifications | nucleosome I n eukaryotes, transcription occurs within the context of a restrictive, yet dynamic, chromatin environment. The posttranslational modification of histones represents a major mechanism by which cells control the structure of chromatin. Some modifications of histones include acetylation, methylation, and ubiquitylation. These modifications can alter the structural properties of nucleosomes and serve as specific effectors for the recruitment of proteins that further modify the chromatin template and regulate transcription (1).Monoubiquitylation of histone H2B on lysine (K) 123 in Saccharomyces cerevisiae is a conserved modification that is enriched on active genes but plays roles in both transcriptional repression and activation (2-4). Consistent with a repressive role, H2B monoubiquitylation stabilizes nucleosomes at yeast promoters (5), inhibits the association of the RNA polymerase (pol) II kinase Ctk1 with genes in yeast (6), and interferes with the recruitment of the elongation factor TFIIS to genes in human cells (7). In other studies, H2B monoubiquitylation has been shown to stimulate transcription of chromatin templates (8), promote nucleosome reassembly during transcription elongation (9), and inhibit chromatin compaction (10). H2B monoubiquitylation is also a prerequisite for other histone modifications that mark active genes. Ubiquitylation of H2B K123 by the Rad6-Bre1 ubiquitin conjugase-ligase proteins in yeast (11-13) is required for dimethylation and trimethylation of H3 K4 and K79 by the Set1/COMPASS and Dot1 methy...

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“…Histone modifications, on the other hand, can influence the properties of the nucleosome to alter chromatin function, or they can act as recognition sites for the binding of non-histone proteins which can alter chromatin structure and function [5]. Indeed, protein subunits of ATP-dependent remodelling complexes can contain domains which display an affinity for chromatin marked by the various histone PTMs thereby targeting chromatin remodelling activities to discrete sites within the genome [6]. …”

Section: Introductionmentioning

confidence: 99%