Publication Date:
2014-08-12
Description:
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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4412442/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4412442/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lara-Astiaso, David -- Weiner, Assaf -- Lorenzo-Vivas, Erika -- Zaretsky, Irina -- Jaitin, Diego Adhemar -- David, Eyal -- Keren-Shaul, Hadas -- Mildner, Alexander -- Winter, Deborah -- Jung, Steffen -- Friedman, Nir -- Amit, Ido -- 1P50HG006193/HG/NHGRI NIH HHS/ -- P50 HG006193/HG/NHGRI NIH HHS/ -- New York, N.Y. -- Science. 2014 Aug 22;345(6199):943-9. doi: 10.1126/science.1256271. Epub 2014 Aug 7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Immunology, Weizmann Institute of Science, Rehovot, Israel. ; Institute of Life Sciences, The Hebrew University, Jerusalem, Israel. School of Computer Science and Engineering, The Hebrew University, Jerusalem, Israel. ; 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. ; Department of Immunology, Weizmann Institute of Science, Rehovot, Israel. nir@cs.huji.ac.il ido.amit@weizmann.ac.il.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25103404" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Cell Lineage/genetics
;
Chromatin/*metabolism
;
Chromatin Immunoprecipitation/methods
;
*Enhancer Elements, Genetic
;
Female
;
Gene Expression Profiling
;
*Gene Expression Regulation
;
Hematopoiesis/*genetics
;
Hematopoietic Stem Cells/cytology/*metabolism
;
Histones/chemistry/metabolism
;
Mice
;
Transcription Factors/*metabolism
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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