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OA北大核心CSTPCD

[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.The polycomb-like prorein(PCL)subunit of PRC2.1 is responsible for recognizing and directing the binding of PRC2.1 to unmethylated CpG sites,while the adipocyte enhancer-binding protein 2(AEBP2)and Jumonji and(A+T)-rich interaction domain-containing protein 2(JARID2)subunits of PRC2.2 mainly bind to the H2AK119ub1 site and catalyze H3K27 methylation at the corresponding site.Here we focus on the dramatic changes in chromatin 3D conformation during pre-implantation embryonic development in mammals(humans and mice)and provide a comprehensive summary of new insights into the mechanistic roles of PRC in these processes.We describe the effects of PRC on chromatin 3D organization in spermatozoa and oocytes prior to fertilization.PRC1 can establish specific long-distance interactions in spermatozoa through chromobox(CBX)and polyhomeotic(PHC)subunits,which compact the chromatin region of the promoters of developmental genes modified by H3K27me3.PRC may be involved in the chromatin 3D organization of the oocytes during oocyte development,including dynamic changes in loops,topological associated domains(TADs),compartments,and other chromatin 3D conformational features.Subsequently,we further introduce the effect of PRC on chromatin 3D assembly at early embryonic developmental stages after fertilization.The effect of PRC on the dynamic changes in chromatin 3D conformation before and after zygotic genome activation(ZGA)during pre-implantation embryonic development after fertilization is significantly different between human and mouse.Compartments in mouse post-fertilization embryos appeared at the two-cell stage and became more pronounced at the eight-cell stage.Human compartments did not strictly enhance with ZGA but did not appear until the morula embryo stage and became pronounced at the blastocyst stage,suggesting that the changes in compartments may not be significantly correlated with ZGA in human.[Perspective]PRC plays an important role in pre-implantation embryos and their derived stem cells,and its spatiotemporal-specific transcriptional regulation throughout all stages of growth and development is an essential component in maintaining the normal function of embryos and stem cells.Considering the complexity of PRC's involvement in transcriptional regulation across various cell types,future research must undertake detailed experimental studies to elucidate the contributions of distinct PRC components in shaping chromatin 3D conformation during embryonic development.It is especially important to explore the compensatory and synergistic functions of various accessory proteins within this context.