An integrative view of the regulatory and transcriptional landscapes in mouse hematopoiesis
An integrative view of the regulatory and transcriptional landscapes in mouse hematopoiesis
Abstract Thousands of epigenomic datasets have been generated in the past decade, but it is difficult for researchers to effectively utilize all the data relevant to their projects. Systematic integrative analysis can help meet this need, and the VISION project was established for ValIdated Systematic IntegratiON of epigenomic data in hematopoiesis. Here, we systematically integrated extensive data recording epigenetic features and transcriptomes from many sources, including individual laboratories and consortia, to produce a comprehensive view of the regulatory landscape of differentiating hematopoietic cell types in mouse. By employing IDEAS as our Integrative and Discriminative Epigenome Annotation System, we identified and assigned epigenetic states simultaneously along chromosomes and across cell types, precisely and comprehensively. Combining nuclease accessibility and epigenetic states produced a set of over 200,000 candidate cis-regulatory elements (cCREs) that efficiently capture enhancers and promoters. The transitions in epigenetic states of these cCREs across cell types provided insights into mechanisms of regulation, including decreases in numbers of active cCREs during differentiation of most lineages, transitions from poised to active or inactive states, and shifts in nuclease accessibility of CTCF-bound elements. Regression modeling of epigenetic states at cCREs and gene expression produced a versatile resource to improve selection of cCREs potentially regulating target genes. These resources are available from our VISION website (usevision.org) to aid research in genomics and hematopoiesis.
Hughes Jim、Taylor James、Cheng Yong、Hardison Ross C.、Keller Cheryl A.、Heuston Elisabeth、An Lin、Weaver Kathryn、G?ttgens Berthold、Bodine David、Lichtenberg Jens、Weiss Mitchell J.、Zhang Yu、Blobel Gerd A.、Higgs Douglas R.、Wixom Alexander Q.、Cockburn April、Mahony Shaun、Giardine Belinda M.、Sauria Michael E.G.、Miller Amber、Li Qunhua、Xiang Guanjue、Yue Feng
MRC Weatherall Institute of Molecular Medicine, Oxford UniversityDepartments of Biology and Computer Science, Johns Hopkins UniversityDepartment of Hematology, St. Jude Children?ˉs Research HospitalDepartment of Biochemistry and Molecular Biology, Program in Bioinformatics and Genomics, Center for Computational Biology and Bioinformatics, The Pennsylvania State UniversityDepartment of Biochemistry and Molecular Biology, Program in Bioinformatics and Genomics, Center for Computational Biology and Bioinformatics, The Pennsylvania State UniversityNHGRI Hematopoiesis Section, Genetics and Molecular Biology Branch, National Institutes of HealthDepartment of Biochemistry and Molecular Biology, Program in Bioinformatics and Genomics, Center for Computational Biology and Bioinformatics, The Pennsylvania State UniversityDepartments of Biology and Computer Science, Johns Hopkins UniversityWelcome and MRC Cambridge Stem Cell Institute, University of CambridgeNHGRI Hematopoiesis Section, Genetics and Molecular Biology Branch, National Institutes of HealthNHGRI Hematopoiesis Section, Genetics and Molecular Biology Branch, National Institutes of HealthDepartment of Hematology, St. Jude Children?ˉs Research HospitalDepartment of Statistics, Program in Bioinformatics and Genomics, Center for Computational Biology and Bioinformatics, The Pennsylvania State UniversityDepartment of Pediatrics, Children?ˉs Hospital of Philadelphia and University of Pennsylvania School of MedicineMRC Weatherall Institute of Molecular Medicine, Oxford UniversityDepartment of Biochemistry and Molecular Biology, Program in Bioinformatics and Genomics, Center for Computational Biology and Bioinformatics, The Pennsylvania State UniversityDepartment of Biochemistry and Molecular Biology, Program in Bioinformatics and Genomics, Center for Computational Biology and Bioinformatics, The Pennsylvania State UniversityDepartment of Biochemistry and Molecular Biology, Program in Bioinformatics and Genomics, Center for Computational Biology and Bioinformatics, The Pennsylvania State UniversityDepartment of Biochemistry and Molecular Biology, Program in Bioinformatics and Genomics, Center for Computational Biology and Bioinformatics, The Pennsylvania State UniversityDepartments of Biology and Computer Science, Johns Hopkins UniversityDepartment of Biochemistry and Molecular Biology, Program in Bioinformatics and Genomics, Center for Computational Biology and Bioinformatics, The Pennsylvania State UniversityDepartment of Statistics, Program in Bioinformatics and Genomics, Center for Computational Biology and Bioinformatics, The Pennsylvania State UniversityDepartment of Biochemistry and Molecular Biology, Program in Bioinformatics and Genomics, Center for Computational Biology and Bioinformatics, The Pennsylvania State UniversityDepartment of Biochemistry and Molecular Biology, The Pennsylvania State University College of Medicine
基础医学生物科学研究方法、生物科学研究技术分子生物学
epigeneticsgene regulatory elementsdimensional reductionregulatory potential
Hughes Jim,Taylor James,Cheng Yong,Hardison Ross C.,Keller Cheryl A.,Heuston Elisabeth,An Lin,Weaver Kathryn,G?ttgens Berthold,Bodine David,Lichtenberg Jens,Weiss Mitchell J.,Zhang Yu,Blobel Gerd A.,Higgs Douglas R.,Wixom Alexander Q.,Cockburn April,Mahony Shaun,Giardine Belinda M.,Sauria Michael E.G.,Miller Amber,Li Qunhua,Xiang Guanjue,Yue Feng.An integrative view of the regulatory and transcriptional landscapes in mouse hematopoiesis[EB/OL].(2025-03-28)[2025-04-24].https://www.biorxiv.org/content/10.1101/731729.点此复制
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