PHF20 readers link methylation of histone H3K4 and p53 with H4K16 acetylation

PHF20 is a core component of the lysine acetyltransferase complex MOF-NSL that produces the major epigenetic mark, H4K16ac, and is necessary for transcriptional regulation and DNA repair, however the role of PHF20 in the complex remains elusive. Here, we report on functional crosstalk between epigenetic readers of PHF20. We show that the PHF20 PHD finger recognizes dimethylated lysine 4 of histone H3 (H3K4me2) and represents first example of a native PHD reader selective for this modification. Biochemical and structural analyses illuminate the molecular mechanism underlying this function and explain the preference of Tudor2, another reader in PHF20, for dimethylated p53. Binding of the PHD finger to H3K4me2 is required for histone acetylation, accumulation of PHF20 at target genes, and transcriptional activation. Together, our findings establish a novel PHF20-mediated link between MOF HAT, p53 and H3K4me2-dependent cellular events and suggest a model for rapid spreading of H4K16ac-encriched open chromatin.PHF20是生成核心表观遗传标记H4K16ac的赖氨酸乙酰转移酶复合物MOF-NSL（lysine acetyltransferase complex MOF-NSL）的核心组分，其在转录调控与DNA修复过程中发挥不可或缺的作用，但PHF20在该复合物中的功能仍尚不明确。本研究探讨了PHF20所包含的表观识别因子之间的功能串扰。研究发现，PHF20的PHD指结构域（PHD finger）可识别组蛋白H3第4位赖氨酸二甲基化（H3K4me2），这是首个天然PHD识别域对该修饰具有选择性的实例。生化与结构分析揭示了该功能的分子机制，并解释了PHF20中另一识别域Tudor2对二甲基化p53的结合偏好性。PHD指结构域与H3K4me2的结合，是组蛋白乙酰化、PHF20在靶基因位点富集以及转录激活的必要条件。综上，本研究揭示了一条由PHF20介导的、连接MOF组蛋白乙酰转移酶（MOF HAT）、p53与依赖H3K4me2的细胞事件的全新调控通路，并提出了H4K16ac富集型开放染色质快速扩散的模型。

搜集汇总

背景与挑战

背景概述

该数据集聚焦PHF20蛋白在表观遗传调控中的作用，通过RNA-Seq技术研究了人类细胞中PHF20如何连接H3K4甲基化、p53和H4K16乙酰化事件。数据集包含6个转录组样本，分为PHF20敲低和对照组，使用Illumina HiSeq 2000平台生成，数据量约37.95 GB，旨在揭示PHF20介导的染色质修饰交叉对话机制。