Divergence of Mammalian Higher Order Chromatin Structure Is Associated with Developmental Loci

Several recent studies have examined different aspects of mammalian higher order chromatin structure – replication timing, lamina association and Hi-C inter-locus interactions — and have suggested that most of these features of genome organisation are conserved over evolution. However, the extent of evolutionary divergence in higher order structure has not been rigorously measured across the mammalian genome, and until now little has been known about the characteristics of any divergent loci present. Here, we generate a dataset combining multiple measurements of chromatin structure and organisation over many embryonic cell types for both human and mouse that, for the first time, allows a comprehensive assessment of the extent of structural divergence between mammalian genomes. Comparison of orthologous regions confirms that all measurable facets of higher order structure are conserved between human and mouse, across the vast majority of the detectably orthologous genome. This broad similarity is observed in spite of many loci possessing cell type specific structures. However, we also identify hundreds of regions (from 100 Kb to 2.7 Mb in size) showing consistent evidence of divergence between these species, constituting at least 10% of the orthologous mammalian genome and encompassing many hundreds of human and mouse genes. These regions show unusual shifts in human GC content, are unevenly distributed across both genomes, and are enriched in human subtelomeric regions. Divergent regions are also relatively enriched for genes showing divergent expression patterns between human and mouse ES cells, implying these regions cause divergent regulation. Particular divergent loci are strikingly enriched in genes implicated in vertebrate development, suggesting important roles for structural divergence in the evolution of mammalian developmental programmes. These data suggest that, though relatively rare in the mammalian genome, divergence in higher order chromatin structure has played important roles during evolution.     

Structure of Lily Glucomannan Deduced from Enzymic Hydrolyzate

A thermostable acetylxylan esterase gene, TTE0866, which catalyzes the deacetylation of cellulose acetate, was cloned from the genome of Caldanaerobacter subterraneus subsp. tengcongensis. The pH and temperature optima were 8.0 and 60 °C. The esterase was inhibited by phenylmethylsulfonyl fluoride. A mixture of the esterase and cellulolytic enzymes efficiently degraded insoluble cellulose acetate with a higher degree of substitution.     

Structure of Chromatin

Physico-chemical experiments show that histones are not evenly distributed in chromatin. About half of the DNA is “open” and not covered with proteins.     

染色质结构之美——染色质可及性

染色质可及性(chromatin accessibility)作为一种衡量染色质结合因子与染色质DNA结合能力高低的染色质属性,是评价染色质结构稳态的重要指标之一,在多种细胞核进程中扮演重要角色,包括基因转录调控以及DNA损伤修复等。该属性的异常调控与多种疾病的发生发展密切相关,包括肿瘤以及神经退行性疾病等。对于该属性探究已经成为生命科学与疾病领域的热点。伴随越来越多的新技术应运而生,例如染色质构象捕获技术、高通量测序技术以及两种技术的结合等。随着技术的进步,多种参与调控染色质可及性的因素被发现和总结,包括核小体占位、组蛋白修饰以及非编码RNA等。多项大规模的染色质组学数据绘制了多种疾病的染色质可及性图谱,为揭示疾病的发生发展与染色质可及性之间的关系提供了数据支持。同时,随着单细胞染色质可及性测序技术的发展,实现了对细胞类型染色质层面的划分,弥补了单纯依赖基因表达划分细胞类型的不足。本文将从染色质的组成与可及性、影响染色质可及性的因素、染色质可及性的检测方法,以及染色质可及性与癌症的关系等方面简要阐述染色质可及性的研究进展。     

Retention of the Native Epigenome in Purified Mammalian Chromatin

A protocol is presented for the isolation of native mammalian chromatin as fibers of 25–250 nucleosomes under conditions that preserve the natural epigenetic signature. The material is composed almost exclusively of histones and DNA and conforms to the structure expected by electron microscopy. All sequences probed for were retained, indicating that the material is representative of the majority of the genome. DNA methylation marks and histone marks resembled the patterns observed in vivo. Importantly, nucleosome positions also remained largely unchanged, except on CpG islands, where nucleosomes were found to be unstable. The technical challenges of reconstituting biochemical reactions with native mammalian chromatin are discussed.     

Inter-Chromosomal Contact Networks Provide Insights into Mammalian Chromatin Organization

The recent advent of conformation capture techniques has provided unprecedented insights into the spatial organization of chromatin. We present a large-scale investigation of the inter-chromosomal segment and gene contact networks in embryonic stem cells of two mammalian organisms: humans and mice. Both interaction networks are characterized by a high degree of clustering of genome regions and the existence of hubs. Both genomes exhibit similar structural characteristics such as increased flexibility of certain Y chromosome regions and co-localization of centromere-proximal regions. Spatial proximity is correlated with the functional similarity of genes in both species. We also found a significant association between spatial proximity and the co-expression of genes in the human genome. The structural properties of chromatin are also species specific, including the presence of two highly interactive regions in mouse chromatin and an increased contact density on short, gene-rich human chromosomes, thereby indicating their central nuclear position. Trans-interacting segments are enriched in active marks in human and had no distinct feature profile in mouse. Thus, in contrast to interactions within individual chromosomes, the inter-chromosomal interactions in human and mouse embryonic stem cells do not appear to be conserved.     

Dynamics of 5-Hydroxymethylcytosine and Chromatin Marks in Mammalian Neurogenesis

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Highlights? 5hmC levels increase in neuronal function-related genes during neurogenesis ? 5hmC gain is accompanied by H3K27me3 loss at promoters and gene bodies ? Gain of 5hmC is not associated with substantial DNA demethylation ? Polycomb and Tet protein together promote proper progression of neurogenesis     

染色质结构与基因表达调控

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Recovering Genetic Regulatory Networks from Chromatin Immunoprecipitation and Steady-State Microarray Data

Recent advances in high-throughput DNA microarrays and chromatin immunoprecipitation (ChIP) assays have enabled the learning of the structure and functionality of genetic regulatory networks. In light of these heterogeneous data sets, this paper proposes a novel approach for reconstruction of genetic regulatory networks based on the posterior probabilities of gene regulations. Built within the framework of Bayesian statistics and computational Monte Carlo techniques, the proposed approach prevents the dichotomy of classifying gene interactions as either being connected or disconnected, thereby it reduces significantly the inference errors. Simulation results corroborate the superior performance of the proposed approach relative to the existing state-of-the-art algorithms. A genetic regulatory network for Saccharomyces cerevisiae is inferred based on the published real data sets, and biological meaningful results are discussed.     

Chitinous Component of the Cell Wall of Fusarium oxysporum,Its Structure Deduced from Chitosanase Digestion

The cell wall of Fusarium oxysporum was digested with commercial Bacillus pumilus chitosanase. The chitosanase produced low molecular weight heterooligosaccharides consisting of GlcN and GlcNAc from the cell wall. A main component of the digestion products was identified as 2-amino-2-deoxy-β-d-glucopyranosyl-(1 →4)-2-acetamido-2-deoxy-d-glucopyranose. The chitosanase appeared to be more effective than Streptomyces griseus chitinase for cell wall digestion. Moreover, maltose was unexpectedly found in the digestion products, indicating that the cell wall contains α-1,4-linked glucan chain as a polysaccharide component.