UBR7 acts as a histone chaperone for post‐nucleosomal histone H3

AbstractBiogenesis of eukaryotic box C/D small nucleolar ribonucleoproteins initiates co-transcriptionally and requires the action of the assembly machinery including the Hsp90/R2TP complex, the Rsa1p:Hit1p heterodimer and the Bcd1 protein. We present genetic interactions between the Rsa1p-encoding gene and genes involved in chromatin organization including RTT106 that codes for the H3-H4 histone chaperone Rtt106p controlling H3K56ac deposition. We show that Bcd1p binds Rtt106p and controls its transcription-dependent recruitment by reducing its association with RNA polymerase II, modulating H3K56ac levels at gene body. We reveal the 3D structures of the free and Rtt106p-bound forms of Bcd1p using nuclear magnetic resonance and X-ray crystallography. The interaction is also studied by a combination of biophysical and proteomic techniques. Bcd1p interacts with a region that is distinct from the interaction interface between the histone chaperone and histone H3. Our results are evidence for a protein interaction interface for Rtt106p that controls its transcription-associated activity.

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Histone transfer among chaperones

Biochemical Society Transactions ◽

10.1042/bst20110737 ◽

2012 ◽

Vol 40 (2) ◽

pp. 357-363 ◽

Cited By ~ 17

Author(s):

Wallace H. Liu ◽

Mair E.A. Churchill

Keyword(s):

Histone H3 ◽

Histone Chaperone ◽

Chromatin Assembly ◽

Histone Chaperones ◽

Nucleosome Assembly ◽

Post Translational Modifications ◽

Chromatin Dynamics ◽

Nucleosomal Dna ◽

Chaperone Interactions ◽

Dependent Processes

The eukaryotic processes of nucleosome assembly and disassembly govern chromatin dynamics, in which histones exchange in a highly regulated manner to promote genome accessibility for all DNA-dependent processes. This regulation is partly carried out by histone chaperones, which serve multifaceted roles in co-ordinating the interactions of histone proteins with modification enzymes, nucleosome remodellers, other histone chaperones and nucleosomal DNA. The molecular details of the processes by which histone chaperones promote delivery of histones among their many functional partners are still largely undefined, but promise to offer insights into epigenome maintenance. In the present paper, we review recent findings on the histone chaperone interactions that guide the assembly of histones H3 and H4 into chromatin. This evidence supports the concepts of histone post-translational modifications and specific histone chaperone interactions as guiding principles for histone H3/H4 transactions during chromatin assembly.

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Structure of the Histone Chaperone Asf1 Bound to the Histone H3 C-Terminal Helix and Functional Insights

Structure ◽

10.1016/j.str.2007.01.002 ◽

2007 ◽

Vol 15 (2) ◽

pp. 191-199 ◽

Cited By ~ 30

Author(s):

Morgane Agez ◽

Jun Chen ◽

Raphaël Guerois ◽

Carine van Heijenoort ◽

Jean-Yves Thuret ◽

...

Keyword(s):

Histone H3 ◽

Histone Chaperone

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Structural basis of nucleosomal histone H4 lysine 20 methylation by SET8 methyltransferase

Life Science Alliance ◽

10.26508/lsa.202000919 ◽

2021 ◽

Vol 4 (4) ◽

pp. e202000919

Author(s):

Cheng-Han Ho ◽

Yoshimasa Takizawa ◽

Wataru Kobayashi ◽

Yasuhiro Arimura ◽

Hiroshi Kimura ◽

...

Keyword(s):

Crystal Structure ◽

Essential Role ◽

Histone H3 ◽

Underlying Mechanism ◽

Structural Basis ◽

Histone H4 ◽

Nucleosomal Histone

SET8 is solely responsible for histone H4 lysine-20 (H4K20) monomethylation, which preferentially occurs in nucleosomal H4. However, the underlying mechanism by which SET8 specifically promotes the H4K20 monomethylation in the nucleosome has not been elucidated. Here, we report the cryo-EM structures of the human SET8–nucleosome complexes with histone H3 and the centromeric H3 variant, CENP-A. Surprisingly, we found that the overall cryo-EM structures of the SET8–nucleosome complexes are substantially different from the previous crystal structure models. In the complexes with H3 and CENP-A nucleosomes, SET8 specifically binds the nucleosomal acidic patch via an arginine anchor, composed of the Arg188 and Arg192 residues. Mutational analyses revealed that the interaction between the SET8 arginine anchor and the nucleosomal acidic patch plays an essential role in the H4K20 monomethylation activity. These results provide the groundwork for understanding the mechanism by which SET8 specifically accomplishes the H4K20 monomethylation in the nucleosome.

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Histone chaperone FACT represses retrotransposon MERVL and MERVL-derived cryptic promoters

Nucleic Acids Research ◽

10.1093/nar/gkaa732 ◽

2020 ◽

Vol 48 (18) ◽

pp. 10211-10225 ◽

Cited By ~ 1

Author(s):

Fuquan Chen ◽

Weiyu Zhang ◽

Dan Xie ◽

Tingting Gao ◽

Zhiqiang Dong ◽

...

Keyword(s):

Target Genes ◽

Critical Role ◽

Histone H3 ◽

Embryonic Stem ◽

Histone Chaperone ◽

Endogenous Retroviruses ◽

Histone Chaperones ◽

Cryptic Transcription ◽

Unique Mechanism ◽

Cryptic Promoters

Abstract Endogenous retroviruses (ERVs) were usually silenced by various histone modifications on histone H3 variants and respective histone chaperones in embryonic stem cells (ESCs). However, it is still unknown whether chaperones of other histones could repress ERVs. Here, we show that H2A/H2B histone chaperone FACT plays a critical role in silencing ERVs and ERV-derived cryptic promoters in ESCs. Loss of FACT component Ssrp1 activated MERVL whereas the re-introduction of Ssrp1 rescued the phenotype. Additionally, Ssrp1 interacted with MERVL and suppressed cryptic transcription of MERVL-fused genes. Remarkably, Ssrp1 interacted with and recruited H2B deubiquitinase Usp7 to Ssrp1 target genes. Suppression of Usp7 caused similar phenotypes as loss of Ssrp1. Furthermore, Usp7 acted by deubiquitinating H2Bub and thereby repressed the expression of MERVL-fused genes. Taken together, our study uncovers a unique mechanism by which FACT complex silences ERVs and ERV-derived cryptic promoters in ESCs.

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