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  Dynamic Control of Enhancer Repertoires Drives Lineage and Stage-Specific Transcription during Hematopoiesis

Huang, J., Liu, X., Li, D., Shao, Z., Cao, H., Zhang, Y., et al. (2016). Dynamic Control of Enhancer Repertoires Drives Lineage and Stage-Specific Transcription during Hematopoiesis. Developmental Cell, 36, 9-23. doi:10.1016/j.devcel.2015.12.014.

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 Creators:
Huang, Jialiang1, Author
Liu, Xin1, Author
Li, Dan1, Author
Shao, Zhen1, Author
Cao, Hui1, Author
Zhang, Yuannyu1, Author
Trompouki, Eirini2, Author              
Bowman, Teresa V.1, Author
Zon, Leonard I.1, Author
Yuan, Guo-Cheng1, Author
Orkin, Stuart H.1, Author
Xu, Jian1, Author
Affiliations:
1External Organizations, ou_persistent22              
2Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society, 79108 Freiburg, DE, ou_2243640              

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 Abstract: Enhancers are the primary determinants of cell identity, but the regulatory components controlling enhancer turnover during lineage commitment remain largely unknown. Here we compare the enhancer landscape, transcriptional factor occupancy, and transcriptomic changes in human fetal and adult hematopoietic stem/progenitor cells and committed erythroid progenitors. We find that enhancers are modulated pervasively and direct lineage- and stage-specific transcription. GATA2-to-GATA1 switch is prevalent at dynamic enhancers and drives erythroid enhancer commissioning. Examination of lineage-specific enhancers identifies transcription factors and their combinatorial patterns in enhancer turnover. Importantly, by CRISPR/Cas9-mediated genomic editing, we uncover functional hierarchy of constituent enhancers within the SLC25A37 super-enhancer. Despite indistinguishable chromatin features, we reveal through genomic editing the functional diversity of several GATA switch enhancers in which enhancers with opposing functions cooperate to coordinate transcription. Thus, genome-wide enhancer profiling coupled with in situ enhancer editing provide critical insights into the functional complexity of enhancers during development.

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Language(s): eng - English
 Dates: 2016-01-11
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1016/j.devcel.2015.12.014
 Degree: -

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Title: Developmental Cell
Source Genre: Journal
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Publ. Info: Cambridge, Mass. : Cell Press
Pages: - Volume / Issue: 36 Sequence Number: - Start / End Page: 9 - 23 Identifier: ISSN: 1534-5807
CoNE: https://pure.mpg.de/cone/journals/resource/111006902714134