The MuvB complex binds and stabilizes nucleosomes downstream of the transcription start site of cell-cycle dependent genes.
The MuvB complex binds and stabilizes nucleosomes downstream of the transcription start site of cell-cycle dependent genes.
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DOI：
10.1038/s41467-022-28094-1
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发表时间：
2022-01-26
影响因子：
16.6
通讯作者：
Rubin SM
中科院分区：
文献类型：
--
作者：
Asthana A;Ramanan P;Hirschi A;Guiley KZ;Wijeratne TU;Shelansky R;Doody MJ;Narasimhan H;Boeger H;Tripathi S;Müller GA;Rubin SM
启动子中的染色质结构被认为调节基因表达，但大多数转录因子（TFs）如何影响核小体位置仍不确定。MuvB - TF复合物调节细胞周期依赖的基因表达，对发育和癌症期间的分化和增殖至关重要。MuvB可正调控和负调控表达，但对MuvB的结构及其生化功能了解甚少。在这里，我们确定了MuvB组装的整体结构和对MuvB基因抑制功能至关重要的亚复合物的晶体结构。我们发现MuvB亚基LIN9和LIN37作为支架蛋白，分别为TF、DNA和组蛋白结合安排其他亚基LIN52、LIN54和RBAP48。生化和结构数据表明，MuvB通过与LIN54-DNA共识位点识别不同的界面结合核小体，并且MuvB增加了核小体在重组启动子中的占用。我们发现，在阻滞细胞中，MuvB主要与MuvB调控基因转录起始位点（TSS）附近的+1核小体紧密结合。这些结果支持了MuvB结合并稳定TSS下游目标启动子上的核小体以抑制基因表达的模型。MuvB蛋白复合物调节细胞周期中差异表达的基因，但其精确的分子功能尚不清楚。在这里，作者揭示了MuvB与细胞周期基因转录起始位点附近的核小体相关，并且该核小体的紧密定位与MuvB依赖性基因抑制相关。
The chromatin architecture in promoters is thought to regulate gene expression, but it remains uncertain how most transcription factors (TFs) impact nucleosome position. The MuvB TF complex regulates cell-cycle dependent gene-expression and is critical for differentiation and proliferation during development and cancer. MuvB can both positively and negatively regulate expression, but the structure of MuvB and its biochemical function are poorly understood. Here we determine the overall architecture of MuvB assembly and the crystal structure of a subcomplex critical for MuvB function in gene repression. We find that the MuvB subunits LIN9 and LIN37 function as scaffolding proteins that arrange the other subunits LIN52, LIN54 and RBAP48 for TF, DNA, and histone binding, respectively. Biochemical and structural data demonstrate that MuvB binds nucleosomes through an interface that is distinct from LIN54-DNA consensus site recognition and that MuvB increases nucleosome occupancy in a reconstituted promoter. We find in arrested cells that MuvB primarily associates with a tightly positioned +1 nucleosome near the transcription start site (TSS) of MuvB-regulated genes. These results support a model that MuvB binds and stabilizes nucleosomes just downstream of the TSS on its target promoters to repress gene expression. The MuvB protein complex regulates genes that are differentially expressed through the cell cycle, yet its precise molecular function has remained unclear. Here the authors reveal MuvB associates with the nucleosome adjacent to the transcription start site of cell-cycle genes and that the tight positioning of this nucleosome correlates with MuvB-dependent gene repression.
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影响因子：
14.9
作者：
Fischer M;Grossmann P;Padi M;DeCaprio JA
通讯作者：
DeCaprio JA
DOI：
10.1007/978-1-4939-1680-1_9
发表时间：
2015-01-01
期刊：
NUCLEUS, 2ND EDITION
影响因子：
--
作者：
Brown, Christopher R.;Eskin, Julian A.;Boeger, Hinrich
通讯作者：
Boeger, Hinrich
DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
影响因子：
16
作者：
Chen S;Jiao L;Shubbar M;Yang X;Liu X
通讯作者：
Liu X
影响因子：
64.8
作者：
Dynlacht, BD
通讯作者：
Dynlacht, BD