多梳蛋白抑制复合体(PRC)在植入前胚胎发育过程中对染色质三维结构重建的影响  

Impact of polycomb repressive complex(PRC)on chromatin 3D structure reconstruction during pre-implantation embryonic development

作　　者：吕晓雯 LÜXiaowen(School of Medicine,Xiamen University,Xiamen 361102,China)

机构地区：[1]厦门大学医学院,福建厦门361102

出　　处：《厦门大学学报（自然科学版）》2024年第5期813-823,共11页Journal of Xiamen University：Natural Science

基　　金：国家重点研发计划(2021YFC2700300,2021YFC2700303);国家自然科学基金(32170546)。

摘　　要：[背景]多细胞生物发育是一个极为复杂而协调的过程,伴随着组织特异性基因的时空特异性表达.近年来,人们逐渐意识到除转录因子及组蛋白翻译后修饰能影响邻近基因的表达外,染色质的三维(3D)结构组装同样对转录发挥重要调控作用.植入前胚胎及胚胎干细胞因具有分化为多种器官组织及持续增殖保持更新的能力,成为研究基因转录调控与染色质3D构象等表观遗传修饰相互作用的重要模型.[进展]多梳蛋白抑制复合体(polycomb repressive complex,PRC)在哺乳动物不同物种中都发挥多种功能,特别是在哺乳动物的植入前胚胎发生过程中其活性及基因组结合位点均发生显著变化.PRC不仅可以通过组蛋白修饰直接参与靶基因的转录调控,也可以协同其他转录因子,通过影响染色质微环境进而参与靶基因转录调控进程.本文重点探讨哺乳动物(人与鼠)的植入前胚胎发育过程中染色质3D构象剧烈变化的规律,并归纳PRC在上述过程中作用机制的新进展.[展望]考虑到PRC在不同细胞中参与转录调控过程的复杂性,未来需要进一步实验来研究PRC的不同组分在胚胎发育过程中细胞染色质3D构象构建中的贡献,特别要注意不同附属蛋白的功能代偿性及协同性.[Background]The development of multicellular organisms is an extremely complex and coordinated process,accompanied by the spatiotemporal-specific expression of tissue-specific genes.In recent years,it has been increasingly recognized that,in addition to transcription factors and post-translational histone modifications,which can affect the expression of adjacent genes,the 3D organization of chromatin also plays a pivotal role in transcriptional regulation.In the highly ordered and folded cell nucleus,the 3D structure of chromatin brings different types of regulatory elements into close proximity to each other,enabling the precise regulation for transcription for linearly distant target genes.Chromatin conformational changes during development are emerging as important regulators that affect cell development and function,providing new perspectives for a more comprehensive and precise understanding of the complexity of life.Pre-implantation embryos and embryonic stem cells,owing to their ability to differentiate into various organ tissues and their capacity for sustained proliferation and renewal,have become essential models for investigating the interplay between gene transcription regulation and epigenetic modifications such as chromatin 3D conformation.[Progress]The polycomb repressive complex(PRC)performs diverse functions across different mammalian species,particularly during pre-implantation embryogenesis in mammals,where its activity and genomic binding sites exhibit significant changes.PRC can directly modulate the transcriptional regulation of target genes through histone modifications and also collaborates with other transcription factors by altering the chromatin microenvironment,thus influencing the transcriptional regulatory process.Among them,classical PRC1 has a minor enzymatic catalytic effect on histones and mainly affects the 3D conformation of chromatin,while non-classical PRC1 can ubiquitinate gene promoters and carry out genome-wide H2AK119 modifications,directly regulating the gene expression.

关 键 词：胚胎发育 染色质三维构象 多梳蛋白抑制复合体 

分 类 号：Q-3[生物学]