生物
抄写(语言学)
核糖核酸
组蛋白H3
组蛋白
染色质
变构调节
遗传学
细胞生物学
DNA
基因
哲学
语言学
受体
作者
Markus Blatter,Charlotte Meylan,Antoine Cléry,Roberto Giambruno,Yaroslav Nikolaev,Michel Heidecker,Jessica Arvindbhai Solanki,Manuel O. Dı́az,Davide Gabellini,Frédéric H.‐T. Allain
出处
期刊:Science Advances
[American Association for the Advancement of Science (AAAS)]
日期:2023-04-21
卷期号:9 (16)
被引量:1
标识
DOI:10.1126/sciadv.adf5330
摘要
Mixed-lineage leukemia 1 (MLL1) is a transcription activator of the HOX family, which binds to specific epigenetic marks on histone H3 through its third plant homeodomain (PHD3) domain. Through an unknown mechanism, MLL1 activity is repressed by cyclophilin 33 (Cyp33), which binds to MLL1 PHD3. We determined solution structures of Cyp33 RNA recognition motif (RRM) free, bound to RNA, to MLL1 PHD3, and to both MLL1 and the histone H3 lysine N6-trimethylated. We found that a conserved α helix, amino-terminal to the RRM domain, adopts three different positions facilitating a cascade of binding events. These conformational changes are triggered by Cyp33 RNA binding and ultimately lead to MLL1 release from the histone mark. Together, our mechanistic findings rationalize how Cyp33 binding to MLL1 can switch chromatin to a transcriptional repressive state triggered by RNA binding as a negative feedback loop.
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