Specific Acetylation Patterns of H2A.Z Form Transient Interactions with the BPTF Bromodomain.
Specific Acetylation Patterns of H2A.Z Form Transient Interactions with the BPTF Bromodomain.
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H2A.Z 的特定乙酰化模式与 BPTF 布罗莫结构域形成瞬时相互作用。
DOI:
10.1021/acs.biochem.7b00648
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发表时间:
2017
期刊:
影响因子:
2.9
通讯作者:
Pomerantz,WilliamCK
中科院分区:
文献类型:
--
作者:
Perell,GabriellaT;Mishra,NeerajK;Sudhamalla,Babu;Ycas,PeterD;Islam,Kabirul;Pomerantz,WilliamCK
Post-translational lysine acetylation of histone tails affects both chromatin accessibility and recruitment of multifunctional bromodomain-containing proteins for modulating transcription. The bromodomain- and PHD finger-containing transcription factor (BPTF) regulates transcription but has also been implicated in high gene expression levels in a variety of cancers. In this report, the histone variant H2A.Z, which replaces H2A in chromatin, is evaluated for its affinity for BPTF with a specific recognition pattern of acetylated lysine residues of the N-terminal tail region. Although BPTF immunoprecipitates H2A.Z-containing nucleosomes, a direct interaction with its bromodomain has not been reported. Using protein-observed fluorine nuclear magnetic resonance (PrOF NMR) spectroscopy, we identified a diacetylation of H2A.Z on lysine residues 4 and 11, with the highest affinity for BPTF with aKdof 780 μM. A combination of subsequent1H NMR Carr–Purcell–Meiboom–Gill experiments and photo-cross-linking further confirmed the specificity of the diacetylation pattern at lysines 4 and 11. Because of an adjacent PHD domain, this transient interaction may contribute to a higher-affinity bivalent interaction. Further evaluation of specificity toward a set of bromodomains, including two BET bromodomains (Brd4 and BrdT) and twoPlasmodium falciparumbromodomains, resulted in one midmicromolar affinity binder,PfGCN5 (Kd= 650 μM). With these biochemical experiments, we have identified a direct interaction of histone H2A.Z with bromodomains with a specific acetylation pattern that further supports the role of H2A.Z in epigenetic regulation.
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影响因子:
4
作者:
Urick AK;Calle LP;Espinosa JF;Hu H;Pomerantz WC
通讯作者:
Pomerantz WC
影响因子:
64.5
作者:
Ruthenburg AJ;Li H;Milne TA;Dewell S;McGinty RK;Yuen M;Ueberheide B;Dou Y;Muir TW;Patel DJ;Allis CD
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Allis CD
影响因子:
23.9
作者:
Hu G;Cui K;Northrup D;Liu C;Wang C;Tang Q;Ge K;Levens D;Crane-Robinson C;Zhao K
通讯作者:
Zhao K
影响因子:
4.5
作者:
Hardy S;Jacques PE;Gévry N;Forest A;Fortin ME;Laflamme L;Gaudreau L;Robert F
通讯作者:
Robert F
影响因子:
12.3
作者:
Ku M;Jaffe JD;Koche RP;Rheinbay E;Endoh M;Koseki H;Carr SA;Bernstein BE
通讯作者:
Bernstein BE