2022年3月17日 · Here, we show that Xist drives non-stoichiometric recruitment of the essential silencing protein SHARP (also known as SPEN) to amplify its abundance across the inactive X, including at regions...

2021年4月21日 · SHARP is a protein of more than 400 kDa that contains four RRMs and a highly conserved C-terminal domain, called SPOC (Spen paralog and ortholog C-terminal domain), which is responsible for mediating the repressive function of SHARP .

2022年3月17日 · New evidence suggests that dimeric foci of Xist seed the formation of large protein assemblies that contain a wide spectrum of proteins, such as SPEN (SHARP), CIZ1, CELF, PTBP1 and components...

We have determined the crystal structure of the region of the human SPEN homolog that contains these RRMs-the SMRT/HDAC1 Associated Repressor Protein (SHARP), at 2.0 Å resolution. SHARP is a co-regulator of the nuclear receptors.

2020年2月5日 · We propose that SPEN acts as a molecular integrator for the initiation of XCI, bridging Xist RNA with the transcription machinery—as well as with nucleosome remodellers and histone...

2020年5月7日 · Spen (also known as SHARP, MINT) is a ~ 400 kDa Xist RNA binding protein (RBP) that contains four canonical RNA binding domains, as well as a SPOC domain to facilitate protein-protein interactions. Spen is a co-repressor that binds to several chromatin remodeling complexes, including histone deacetylases (HDACs), and the NuRD complex ( McHugh ...

2020年2月6日 · SPEN是一个非常大的蛋白（大约400kDa），包含四个RNA识别结构域 (RRM)，一个细胞核受体互作结构域（Nuclear receptor interaction domain, RID）以及一个SPOC (SPEN paralogue/orthologue C-terminal)结构域。 其中RRM2-4对于SPEN的招募以及基因沉默非常关键，这与前人在体外进行的实验结果是一致的【8】。 而SPOC的敲除虽然对于SPEN的招募被没有什么影响，但是却显著影响X染色体失活。 这说明，SPOC对于X染色体失活过程非常关 …

2021年4月1日 · Subsequently, Xist is bound by the corepressor SHARP/SPEN, recruiting and/or activating histone deacetylases (HDACs), leading to the loss of active chromatin marks such as H3K27ac. In addition, polycomb complexes PRC1 and PRC2 establish wide-spread accumulation of H3K27me3 and H2AK119ub1 chromatin marks.

我们报告了 SHARP (SPEN) SPOC-CTD 的晶体结构，并确定了其与磷酸化丝氨酸 5 特异性结合的分子决定因素。 PHF3 和 DIDO SPOC 结构域优先与 Pol II 延伸复合物相互作用，而 RBM15 和 SHARP SPOC 结构域与 m6A 写入器和读取器蛋白结合。 我们的研究结果将 SPOC 域确立为转录机制与转录和共转录 过程的调节器之间的主要接口。 RNA 聚合酶 II (Pol II) 的 C 末端结构域 (CTD) 的七重复在整个转录周期中被广泛修饰。 CTD 通过招募转录调节因子以及 RNA 加帽、 …

Here, we show that Xist drives non-stoichiometric recruitment of the essential silencing protein SHARP (also known as SPEN) to amplify its abundance across the inactive X, including at regions not directly occupied by Xist.