Chromatin state dynamics during blood formation

Astiaso, David Lara Astiaso; Assaf Weiner; Vivas, Erika Lorenzo Vivas; Irina Zaretsky; Diego Adhemar Jaitin; Eyal David; Hadas Keren-Shaul; Alexander Mildner; Deborah Winter; Steffen Jung; Nir Friedman; Ido Amit

doi:10.1126/science.1256271

Chromatin state dynamics during blood formation

Astiaso, David Lara Astiaso, Assaf Weiner, Vivas, Erika Lorenzo Vivas, Irina Zaretsky, Diego Adhemar Jaitin, Eyal David, Hadas Keren-Shaul, Alexander Mildner, Deborah Winter, Steffen Jung, Nir Friedman, Ido Amit

Department of Systems Immunology

Research output: Contribution to journal › Article › peer-review

601 Citations (Scopus)

Abstract

Chromatin modifications are crucial for development, yet little is known about their dynamics during differentiation. Hematopoiesis provides a well-defined model to study chromatin state dynamics; however, technical limitations impede profiling of homogeneous differentiation intermediates. We developed a high-sensitivity indexing-first chromatin immunoprecipitation approach to profile the dynamics of four chromatin modifications across 16 stages of hematopoietic differentiation. We identify 48,415 enhancer regions and characterize their dynamics.We find that lineage commitment involves de novo establishment of 17,035 lineage-specific enhancers. These enhancer repertoire expansions foreshadow transcriptional programs in differentiated cells. Combining our enhancer catalog with gene expression profiles, we elucidate the transcription factor network controlling chromatin dynamics and lineage specification in hematopoiesis. Together, our results provide a comprehensive model of chromatin dynamics during development.

Original language	English
Pages (from-to)	943-949
Number of pages	7
Journal	Science
Volume	345
Issue number	6199
DOIs	https://doi.org/10.1126/science.1256271
Publication status	Published - 22 Aug 2014

Funding

European Research Council [309788, 340712]; Israeli Science Foundation [1782/11]; Human Frontier Science Program, Career Development Award [CDA00028/2011-c]; European Molecular Biology Organization; National Human Genome Research Institute Center for Excellence in Genome Science [1P50HG006193]; Israeli Centers of Research Excellence (I-CORE)We thank members of the Amit and Friedman laboratories for critical discussions. We thank G. Brodsky for artwork. This work was supported by grants from the European Research Council (nos. 309788 and 340712), the Israeli Science Foundation (1782/11), the Human Frontier Science Program, Career Development Award (CDA00028/2011-c) (I. A.), a European Molecular Biology Organization Young Investigator Award (I. A.), the National Human Genome Research Institute Center for Excellence in Genome Science (1P50HG006193), and the Israeli Centers of Research Excellence (I-CORE). RNA-seq, ChIP-seq, and ATAC-seq data are deposited in the Gene Expression Omnibus under accession number GSE60103. The data can be viewed from the following Web site: http://compbio.cs.huji.ac.il/blood-chromatin/index.html. A patent application for iChIP has been filed by Yeda, Weizmann Institute of Science, Israel.

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10.1126/science.1256271

Cite this

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title = "Chromatin state dynamics during blood formation",

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AU - Lara Astiaso, Astiaso, David

AU - Weiner, Assaf

AU - Lorenzo Vivas, Vivas, Erika

AU - Zaretsky, Irina

AU - Jaitin, Diego Adhemar

AU - David, Eyal

AU - Keren-Shaul, Hadas

AU - Mildner, Alexander

AU - Winter, Deborah

AU - Jung, Steffen

AU - Friedman, Nir

AU - Amit, Ido

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Chromatin state dynamics during blood formation

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