PHF13 is a molecular reader and transcriptional co-regulator of H3K4me2/3
PHF13 is a molecular reader and transcriptional co-regulator of H3K4me2/3
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DOI：
10.7554/elife.10607
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发表时间：
2016-05-25
期刊：
影响因子：
7.7
通讯作者：
Kinkley, Sarah
中科院分区：
文献类型：
--
作者：
Chung, Ho-Ryun;Xu, Chao;Kinkley, Sarah
PHF 13是一种染色质附属蛋白，在分化、细胞分裂、DNA损伤反应和更高的染色质有序化中具有功能作用。为了深入了解PHF 13调节这些过程的能力，我们阐明了PHF 13靶向染色质的机制，其全基因组定位及其分子染色质背景。尺寸排阻色谱法、质谱法、X射线晶体学和ChIP测序证明PHF 13通过与H3 K4 me 2/3和DNA的直接相互作用以及通过与PRC 2和RNA Polll的相互作用以多价方式结合染色质。此外，PHF 13缺失破坏了PRC 2、RNA Polll S5 P、H3 K4 me 3和H3 K27 me 3之间的相互作用，并导致在转录调节、DNA结合、细胞周期、分化和染色质组织中功能丰富的基因的上调和下调。总之，我们的研究结果表明，PHF 13是一个H3 K4 me 2/3分子阅读器和转录辅助调节因子，使其能够影响不同的染色质过程。
PHF13 is a chromatin affiliated protein with a functional role in differentiation, cell division, DNA damage response and higher chromatin order. To gain insight into PHF13's ability to modulate these processes, we elucidate the mechanisms targeting PHF13 to chromatin, its genome wide localization and its molecular chromatin context. Size exclusion chromatography, mass spectrometry, X-ray crystallography and ChIP sequencing demonstrate that PHF13 binds chromatin in a multivalent fashion via direct interactions with H3K4me2/3 and DNA, and indirectly via interactions with PRC2 and RNA Polll. Furthermore, PHF13 depletion disrupted the interactions between PRC2, RNA Polll S5P, H3K4me3 and H3K27me3 and resulted in the up and down regulation of genes functionally enriched in transcriptional regulation, DNA binding, cell cycle, differentiation and chromatin organization. Together our findings argue that PHF13 is an H3K4me2/3 molecular reader and transcriptional co-regulator, affording it the ability to impact different chromatin processes.