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Systematic integration of GATA transcription factors and epigenomes via IDEAS paints the regulatory landscape of mouse hematopoietic cells

View ORCID ProfileRoss C. Hardison, Yu Zhang, Cheryl A. Keller, View ORCID ProfileGuanjue Xiang, View ORCID ProfileElisabeth Heuston, View ORCID ProfileLin An, View ORCID ProfileJens Lichtenberg, View ORCID ProfileBelinda M. Giardine, David Bodine, View ORCID ProfileShaun Mahony, View ORCID ProfileQunhua Li, View ORCID ProfileFeng Yue, Mitchell J. Weiss, View ORCID ProfileGerd Blobel, View ORCID ProfileJames Taylor, View ORCID ProfileJim Hughes, View ORCID ProfileDoug Higgs, View ORCID ProfileBerthold Gottgens
doi: https://doi.org/10.1101/730358
Ross C. Hardison
The Pennsylvania State University, University Park, PA
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  • For correspondence: rch8@psu.edu
Yu Zhang
The Pennsylvania State University, University Park, PA
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Cheryl A. Keller
The Pennsylvania State University, University Park, PA
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Guanjue Xiang
The Pennsylvania State University, University Park, PA
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Elisabeth Heuston
National Institutes of Health, NHGRI, Bethesda, MD
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Lin An
The Pennsylvania State University, University Park, PA
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Jens Lichtenberg
National Institutes of Health, NHGRI, Bethesda, MD
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Belinda M. Giardine
The Pennsylvania State University, University Park, PA
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David Bodine
National Institutes of Health, NHGRI, Bethesda, MD
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Shaun Mahony
The Pennsylvania State University, University Park, PA
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Qunhua Li
The Pennsylvania State University, University Park, PA
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Feng Yue
The Pennsylvania State University College of Medicine, Hershey, PA
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Mitchell J. Weiss
St. Jude Children’s Research Hospital, Memphis, TN
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Gerd Blobel
Children’s Hospital of Philadelphia, Philadelphia, PA
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James Taylor
Johns Hopkins University, Baltimore, MD
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Jim Hughes
Weatherall Institute of Molecular Medicine, Oxford University, Oxford, UK
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Doug Higgs
Weatherall Institute of Molecular Medicine, Oxford University, Oxford, UK
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Berthold Gottgens
Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK
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Summary

Members of the GATA family of transcription factors play key roles in the differentiation of specific cell lineages by regulating the expression of target genes. Three GATA factors play distinct roles in hematopoietic differentiation. In order to better understand how these GATA factors function to regulate genes throughout the genome, we are studying the epigenomic and transcriptional landscapes of hematopoietic cells in a model-driven, integrative fashion. We have formed the collaborative multi-lab VISION project to conduct ValIdated Systematic IntegratiON of epigenomic data in mouse and human hematopoiesis. The epigenomic data included nuclease accessibility in chromatin, CTCF occupancy, and histone H3 modifications for twenty cell types covering hematopoietic stem cells, multilineage progenitor cells, and mature cells across the blood cell lineages of mouse. The analysis used the Integrative and Discriminative Epigenome Annotation System (IDEAS), which learns all common combinations of features (epigenetic states) simultaneously in two dimensions - along chromosomes and across cell types. The result is a segmentation that effectively paints the regulatory landscape in readily interpretable views, revealing constitutively active or silent loci as well as the loci specifically induced or repressed in each stage and lineage. Nuclease accessible DNA segments in active chromatin states were designated candidate cis-regulatory elements in each cell type, providing one of the most comprehensive registries of candidate hematopoietic regulatory elements to date. Applications of VISION resources are illustrated for regulation of genes encoding GATA1, GATA2, GATA3, and Ikaros. VISION resources are freely available from our website http://usevision.org.

Footnotes

  • http://usevision.org

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Posted August 26, 2019.
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Systematic integration of GATA transcription factors and epigenomes via IDEAS paints the regulatory landscape of mouse hematopoietic cells
Ross C. Hardison, Yu Zhang, Cheryl A. Keller, Guanjue Xiang, Elisabeth Heuston, Lin An, Jens Lichtenberg, Belinda M. Giardine, David Bodine, Shaun Mahony, Qunhua Li, Feng Yue, Mitchell J. Weiss, Gerd Blobel, James Taylor, Jim Hughes, Doug Higgs, Berthold Gottgens
bioRxiv 730358; doi: https://doi.org/10.1101/730358
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Systematic integration of GATA transcription factors and epigenomes via IDEAS paints the regulatory landscape of mouse hematopoietic cells
Ross C. Hardison, Yu Zhang, Cheryl A. Keller, Guanjue Xiang, Elisabeth Heuston, Lin An, Jens Lichtenberg, Belinda M. Giardine, David Bodine, Shaun Mahony, Qunhua Li, Feng Yue, Mitchell J. Weiss, Gerd Blobel, James Taylor, Jim Hughes, Doug Higgs, Berthold Gottgens
bioRxiv 730358; doi: https://doi.org/10.1101/730358

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