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Mixed secondary chromatin structure revealed by modeling radiation-induced DNA fragment length distribution

Science China(Life Sciences) 2020年第6期63卷 825-834页

作者： Wenzong Ma Chenyang Gu Lin Ma Caoqi Fan Chao Zhang Yujie Sun Cheng Li Gen Yang State Key Laboratory of Nuclear Physics and Technology School of PhysicsPeking UniversityBejing 100871China Radiation Biology Center Graduate School of BiostudiesKyoto UniversityKyoto 606-8501Japan Medical Artificial Intelligence and Automation Department of Radiation OncologyUniversity of Texas Southwestern Medical CenterDallasTX 75390USA Center for Bioinformatics School of Life Sciences and Center for Statistical SciencePeking UniversityBejing 100871China State Key Laboratory of Membrane Biology School of Life Sciencesand Biomedical Pioneering Innovation Center(BIOPIC)Peking UniversityBejing 100871China

Spatial chromatin structure plays fundamental roles in many vital biological processes including DNA replication, transcription,damage and repair. However, the current understanding of the secondary structure of chromatin formed by local nucleosomenucleosome interactions remains controversial, especially for the existence and conformation of 30 nm structure. Since chromatin structure influences the fragment length distribution(FLD) of ionizing radiation-induced DNA strand breaks, a 3D chromatin model fitting FLD patterns can help to distinguish different models of chromatin structure. Here, we developed a novel "30-C" model combining 30 nm chromatin structure models with Hi-C data, which measured the spatial contact frequency between different loci in the genome. We first reconstructed the 3D coordinates of the 25 kb bins from Hi-C heatmaps. Within the25 kb bins, lower level chromatin structures supported by recent studies were filled. Simulated FLD patterns based on the 30-C model were compared to published FLD patterns induced by heavy ion radiation to validate the models. Importantly, the 30-C model predicted that the most probable chromatin fiber structure for human interphase fibroblasts in vivo was 45% zig-zag 30 nm fibers and 55% 10 nm fibers.

关键词： Hi-C DNA strand break ionizing radiation chromatin structure

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Noncoding RNA-chromatin association:Functions and mechanisms

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Fundamental Research 2023年第5期3卷 665-675页

作者： Yafei Yin Xiaohua Shen Department of Cell Biology and Department of Cardiology of the Second Affiliated Hospital Zhejiang University School of MedicineYuhangtang RoadHangzhouZhejiang 310058China Tsinghua-Peking Center for Life Sciences School of Medicine and School of Life SciencesTsinghua UniversityBeijing 100084China

Pervasive transcription of the mammalian genome produces hundreds of thousands of noncoding RNAs(ncRNAs).Numerous studies have suggested that some of these ncRNAs regulate multiple cellular processes and play important roles in physiological and pathological ***,a large subset of ncRNAs is enriched on chromatin and participates in regulating gene expression and the dynamics of chromatin structure and *** this review,we summarize recent advances in the functional study of chromatin-associated ncRNAs and mechanistic insights into how these ncRNAs associate with *** also discuss the potential future challenges which still need to be overcome in this field.

关键词： ncRNAs chromatin association Gene expression regulation chromatin structure Repetitive RNAs

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DNA cytosine methylation in plant development

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Journal of Genetics and Genomics 2010年第1期37卷 1-12页

作者： Meishan Zhang Josphert N.Kimatu Kezhang Xu Bao Liu Key Laboratory of Molecular Epigenetics of MOE and Institute of Genetics and Cytology Northeast Normal UniversityChangchun 130024China Department of Agronomy Jilin Agricultural UniversityChangchun 130118China

Cytosine bases of the nuclear genome in higher plants are often extensively *** methylation has been implicated in the silencing of both transposable elements （TEs） and endogenous genes,and loss of methylation may have severe functional *** recent methylation profiling of the entire Arabidopsis genome has provided novel insights into the extent and pattern of cytosine methylation and its relationships with gene *** addition,the fresh studies also revealed the more dynamic nature of this epigenetic modification across plant development than previously *** methylation of gene promoter regions usually inhibits transcription,but methylation in coding regions （gene-body methylation） does not generally affect gene *** demethylation （though probably act synergistically with passive loss of methylation） of promoters by the 5-methyl cytosine DNA glycosylase or DEMETER （DME） is required for the uni-parental expression of imprinting genes in endosperm,which is essential for seed *** opinion that cytosine methylation is indispensible for normal plant development has been reinforced by using single or combinations of diverse loss-of-function mutants for DNA methyltransferases,DNA glycosylases,components involved in siRNA biogenesis and chromatin remodeling *** of cytosine methylation in plants are usually faithfully maintained across organismal generations by the concerted action of epigenetic inheritance and progressive correction of strayed ***,some variant methylation patterns may escape from being corrected and hence produce novel epialleles in the affected somatic ***,coupled with the unique property of plants to produce germline cells late during development,may enable the newly acquired epialleles to be inherited to future generations,which if visible to selection may contribute to adaptation and evolution.

关键词： DNA cytosine methylation alteration DNA methyltransferase DNA glycosylase chromatin structure imprinting plant development

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A Brief Review on the Human Encyclopedia of DNA Elements (ENCODE) Project

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Genomics, Proteomics & Bioinformatics 2013年第3期11卷 135-141页

作者： Hongzhu Qu Xiangdong Fang CAS Key Laboratory of Genome Sciences and Information Beijing Institute of Genomics Chinese Academy of Sciences

The ENCyclopedia Of DNA Elements （ENCODE） project is an international research consortium that aims to identify all functional elements in the human genome sequence. The second phase of the project comprised 1640 datasets from 147 different cell types, yielding a set of 30 publications across several journals. These data revealed that 80.4% of the human genome displays some functionality in at least one cell type. Many of these regulatory elements are physically asso- ciated with one another and further form a network or three-dimensional conformation to affect gene expression. These elements are also related to sequence variants associated with diseases or traits. All these findings provide us new insights into the organization and regulation of genes and genome, and serve as an expansive resource for understanding human health and disease.

关键词： ENCODE project chromatin structure Transcription factors DNA methylation

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Toward an understanding of the relation between gene regulation and 3D genome organization

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Quantitative Biology 2020年第4期8卷 295-311页

作者： Hao Tian Ying Yang Sirui Liu Hui Quan Yi Qin Gao Beijing National Laboratory for Molecular Sciences College of Chemistry and Molecular EngineeringPeking UniversityBeijing 100871China Biomedical Pioneering Innovation Center(BIOPIC) Peking UniversityBeijing 100871China Beijing Advanced Innovation Center for Genomics(ICG) Peking UniversityBeijing 100871China

Background:High-order chromatin structure has been shown to play a vital role in gene *** we identified two types of sequence domains,CGI(CpG island)forest and CGI prairie,which tend to spatially segregate,but to different extent in different *** we aim to further quantify the association of domain segregation with gene regulation and therefore ***:By means of the published RNA-seq and Hi-C data,we identified tissue-specific genes and quantitatively investigated how their regulation is relevant to chromatin ***,two types of gene networks were constructed and the association between gene pair co-regulation and genome organization is ***:We show that compared to forests,tissue-specific genes tend to be enriched in *** specific genes also tend to cluster according to their functions in a relatively small number of ***,tissue-specific forest-prairie contact formation was associated with the regulation of tissue-specific genes,in particular those in the prairie domains,pointing to the important role of gene positioning,in the linear DNA sequence as well as in 3D chromatin structure,in gene regulatory network ***:We investigated how gene regulation is related to genome organization from the perspective of forest-prairie spatial *** unlike compartments A and B,forest and prairie are identified solely based on sequence ***,the simple and uniform framework(forest-prairie domain segregation)provided here can be utilized to further understand the chromatin structure changes as well as the underlying biological significances in different stages,such as tumorgenesis.

关键词： CGI forest CGI prairie domain segregation chromatin structure gene regulation

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