TY - JOUR
T1 - Chromatin state dynamics during blood formation
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
N1 - 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.
PY - 2014/8/22
Y1 - 2014/8/22
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84907419194&partnerID=8YFLogxK
U2 - 10.1126/science.1256271
DO - 10.1126/science.1256271
M3 - مقالة
C2 - 25103404
SN - 0036-8075
VL - 345
SP - 943
EP - 949
JO - Science
JF - Science
IS - 6199
ER -