Author
Zhibin Wang
Other affiliations: Hubei University, North China Electric Power University, National Institutes of Health
Bio: Zhibin Wang is an academic researcher from Johns Hopkins University. The author has contributed to research in topics: Perovskite (structure) & Histone. The author has an hindex of 30, co-authored 65 publications receiving 14743 citations. Previous affiliations of Zhibin Wang include Hubei University & North China Electric Power University.
Papers
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TL;DR: High-resolution maps for the genome-wide distribution of 20 histone lysine and arginine methylations as well as histone variant H2A.Z, RNA polymerase II, and the insulator binding protein CTCF across the human genome using the Solexa 1G sequencing technology are generated.
6,488 citations
TL;DR: The data suggest that a large number of histone modifications may act cooperatively to prepare chromatin for transcriptional activation and be associated with promoters and enhancers.
Abstract: Histones are characterized by numerous posttranslational modifications that influence gene transcription. However, because of the lack of global distribution data in higher eukaryotic systems, the extent to which gene-specific combinatorial patterns of histone modifications exist remains to be determined. Here, we report the patterns derived from the analysis of 39 histone modifications in human CD4(+) T cells. Our data indicate that a large number of patterns are associated with promoters and enhancers. In particular, we identify a common modification module consisting of 17 modifications detected at 3,286 promoters. These modifications tend to colocalize in the genome and correlate with each other at an individual nucleosome level. Genes associated with this module tend to have higher expression, and addition of more modifications to this module is associated with further increased expression. Our data suggest that these histone modifications may act cooperatively to prepare chromatin for transcriptional activation.
2,239 citations
TL;DR: It is found that nucleosome phasing relative to the transcription start sites is directly correlated to RNA polymerase II (Pol II) binding and the first nucleosomes downstream of a start site exhibits differential positioning in active and silent genes.
1,354 citations
TL;DR: In this paper, a genome-wide mapping of HATs and deacetylases binding on chromatin was performed and it was found that both are found at active genes with acetylated histones.
1,244 citations
TL;DR: This study shows in mouse ES cells that Tet1 is preferentially bound to CpG-rich sequences at promoters of both transcriptionally active and Polycomb-repressed genes, and reveals a dual function of Tet1 in promoting transcription of pluripotency factors as well as participating in the repression ofPolycomb-targeted developmental regulators.
Abstract: The modified DNA base 5-hydroxymethylcytosine (5hmC), sometimes called the sixth base, is present in the mammalian genome where it is generated by oxidation of 5-methylcytosine (5mC; the fifth base) by enzymes of the Tet family. Four papers in this issue, from the Helin, Zhang, Rao and Reik laboratories, respectively, report on the genome-wide distribution of Tet1 and/or 5hmC in mouse embryonic stem cells using the ChIP-seq technique. Links between Tet1 and transcription regulation — both activation and repression — are revealed. Anjana Rao and colleagues also describe two alternative methods with increased sensitivity for mapping single 5hmC bases. In the associated News & Views, Nathalie Veron and Antoine H. F. M. Peters discuss what these and other recent papers reveal about the role of Tet proteins in regulating DNA methylation and gene expression. Epigenetic modification of the mammalian genome by DNA methylation (5-methylcytosine) has a profound impact on chromatin structure, gene expression and maintenance of cellular identity1. The recent demonstration that members of the Ten-eleven translocation (Tet) family of proteins can convert 5-methylcytosine to 5-hydroxymethylcytosine raised the possibility that Tet proteins are capable of establishing a distinct epigenetic state2,3. We have recently demonstrated that Tet1 is specifically expressed in murine embryonic stem (ES) cells and is required for ES cell maintenance2. Using chromatin immunoprecipitation coupled with high-throughput DNA sequencing, here we show in mouse ES cells that Tet1 is preferentially bound to CpG-rich sequences at promoters of both transcriptionally active and Polycomb-repressed genes. Despite an increase in levels of DNA methylation at many Tet1-binding sites, Tet1 depletion does not lead to downregulation of all the Tet1 targets. Interestingly, although Tet1-mediated promoter hypomethylation is required for maintaining the expression of a group of transcriptionally active genes, it is also involved in repression of Polycomb-targeted developmental regulators. Tet1 contributes to silencing of this group of genes by facilitating recruitment of PRC2 to CpG-rich gene promoters. Thus, our study not only establishes a role for Tet1 in modulating DNA methylation levels at CpG-rich promoters, but also reveals a dual function of Tet1 in promoting transcription of pluripotency factors as well as participating in the repression of Polycomb-targeted developmental regulators.
642 citations
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TL;DR: The Encyclopedia of DNA Elements project provides new insights into the organization and regulation of the authors' genes and genome, and is an expansive resource of functional annotations for biomedical research.
Abstract: The human genome encodes the blueprint of life, but the function of the vast majority of its nearly three billion bases is unknown. The Encyclopedia of DNA Elements (ENCODE) project has systematically mapped regions of transcription, transcription factor association, chromatin structure and histone modification. These data enabled us to assign biochemical functions for 80% of the genome, in particular outside of the well-studied protein-coding regions. Many discovered candidate regulatory elements are physically associated with one another and with expressed genes, providing new insights into the mechanisms of gene regulation. The newly identified elements also show a statistical correspondence to sequence variants linked to human disease, and can thereby guide interpretation of this variation. Overall, the project provides new insights into the organization and regulation of our genes and genome, and is an expansive resource of functional annotations for biomedical research.
13,548 citations
TL;DR: This work presents Model-based Analysis of ChIP-Seq data, MACS, which analyzes data generated by short read sequencers such as Solexa's Genome Analyzer, and uses a dynamic Poisson distribution to effectively capture local biases in the genome, allowing for more robust predictions.
Abstract: We present Model-based Analysis of ChIP-Seq data, MACS, which analyzes data generated by short read sequencers such as Solexa's Genome Analyzer. MACS empirically models the shift size of ChIP-Seq tags, and uses it to improve the spatial resolution of predicted binding sites. MACS also uses a dynamic Poisson distribution to effectively capture local biases in the genome, allowing for more robust predictions. MACS compares favorably to existing ChIP-Seq peak-finding algorithms, and is freely available.
13,008 citations
TL;DR: It is demonstrated in macrophages and B cells that collaborative interactions of the common factor PU.1 with small sets of macrophage- or B cell lineage-determining transcription factors establish cell-specific binding sites that are associated with the majority of promoter-distal H3K4me1-marked genomic regions.
9,620 citations
Journal Article•
TL;DR: The Encyclopedia of DNA Elements project provides new insights into the organization and regulation of the authors' genes and genome, and is an expansive resource of functional annotations for biomedical research.
Abstract: The human genome encodes the blueprint of life, but the function of the vast majority of its nearly three billion bases is unknown. The Encyclopedia of DNA Elements (ENCODE) project has systematically mapped regions of transcription, transcription factor association, chromatin structure and histone modification. These data enabled us to assign biochemical functions for 80% of the genome, in particular outside of the well-studied protein-coding regions. Many discovered candidate regulatory elements are physically associated with one another and with expressed genes, providing new insights into the mechanisms of gene regulation. The newly identified elements also show a statistical correspondence to sequence variants linked to human disease, and can thereby guide interpretation of this variation. Overall, the project provides new insights into the organization and regulation of our genes and genome, and is an expansive resource of functional annotations for biomedical research.
8,106 citations
TL;DR: In situ Hi-C is used to probe the 3D architecture of genomes, constructing haploid and diploid maps of nine cell types, identifying ∼10,000 loops that frequently link promoters and enhancers, correlate with gene activation, and show conservation across cell types and species.
5,945 citations