title: Immunogenetics. Chromatin state dynamics during blood formation.
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.
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: David
authors.initials: D
authors.lastname: Lara-Astiaso
authors.affiliation: Institute of Life Sciences, The Hebrew University, Jerusalem, Israel. School of Computer Science and Engineering, The Hebrew University, Jerusalem, Israel.
authors.forename: Assaf
authors.initials: A
authors.lastname: Weiner
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Erika
authors.initials: E
authors.lastname: Lorenzo-Vivas
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Irina
authors.initials: I
authors.lastname: Zaretsky
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Diego Adhemar
authors.initials: DA
authors.lastname: Jaitin
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Eyal
authors.initials: E
authors.lastname: David
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Hadas
authors.initials: H
authors.lastname: Keren-Shaul
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Alexander
authors.initials: A
authors.lastname: Mildner
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Deborah
authors.initials: D
authors.lastname: Winter
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Steffen
authors.initials: S
authors.lastname: Jung
authors.affiliation: Institute of Life Sciences, The Hebrew University, Jerusalem, Israel. School of Computer Science and Engineering, The Hebrew University, Jerusalem, Israel. nir@cs.huji.ac.il ido.amit@weizmann.ac.il.
authors.forename: Nir
authors.initials: N
authors.lastname: Friedman
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot, Israel. nir@cs.huji.ac.il ido.amit@weizmann.ac.il.
authors.forename: Ido
authors.initials: I
authors.lastname: Amit
mesh_terms: D000818:Animals; D019070:Cell Lineage / Q000235:genetics; D002843:Chromatin / Q000378:metabolism*; D047369:Chromatin Immunoprecipitation / Q000379:methods; D004742:Enhancer Elements, Genetic; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006410:Hematopoiesis / Q000235:genetics*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism*; D006657:Histones / Q000737:chemistry / Q000378:metabolism; D051379:Mice; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D002843:Chromatin; D006657:Histones; D014157:Transcription Factors
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