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Hematopoietic Signaling Mechanism Revealed from a Stem/Progenitor Cell Cistrome

Cited 24 time in webofscience Cited 26 time in scopus
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Title
Hematopoietic Signaling Mechanism Revealed from a Stem/Progenitor Cell Cistrome
Author(s)
Kyle J. Hewitt; Duk Hyoung Kim; Prithvia Devadas; Rajalekshmi Prathibha; Chandler Zuo; Rajendran Sanalkumar; Kirby D Johnson; Yoon-A Kang; Jin Soo Kim; Colin N. Dewey; Sunduz Keles; Emery H. Bresnick
Publication Date
2015-07
Journal
MOLECULAR CELL, v.59, no.1, pp.62 - 74
Publisher
CELL PRESS
Abstract
Thousands of cis-elements in genomes are predicted to have vital functions. Although conservation, activity in surrogate assays, polymorphisms, and disease mutations provide functional clues, deletion from endogenous loci constitutes the gold-standard test. A GATA-2-binding, Gata2 intronic cis-element (+9.5) required for hematopoietic stem cell genesis in mice is mutated in a human immunodeficiency syndrome. Because +9.5 is the only cis-element known to mediate stem cell genesis, we devised a strategy to identify functionally comparable enhancers (‘‘+9.5-like’’) genome-wide. Gene editing revealed +9.5-like activity to mediate GATA-2 occupancy, chromatin opening, and transcriptional activation. A +9.5-like element resided in Samd14, which encodes a protein of unknown function. Samd14 increased hematopoietic progenitor levels/activity and promoted signaling by a pathway vital for hematopoietic stem/progenitor cell regulation (stem cell factor/c-Kit), and c-Kit rescued Samd14 lossof- function phenotypes. Thus, the hematopoietic stem/progenitor cell cistrome revealed a mediator of a signaling pathway that has broad importance for stem/progenitor cell biology. (c) 2015 Elsevier Inc.
URI
https://pr.ibs.re.kr/handle/8788114/2342
DOI
10.1016/j.molcel.2015.05.020
ISSN
1097-2765
Appears in Collections:
Center for Genome Engineering(유전체 교정 연구단) > 1. Journal Papers (저널논문)
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