Hematopoietic Signaling Mechanism Revealed from a Stem/Progenitor Cell Cistrome

Cited 16 time in webofscience Cited 0 time in scopus
298 Viewed 4 Downloaded
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
ISSN
1097-2765
Appears in Collections:
Center for Genome Engineering(유전체 교정 연구단) > Journal Papers (저널논문)
Files in This Item:
1506_Hematopoietic Signaling Mechanism Revealed from a Stem-Progenitor Cell Cistrome.pdfDownload

qrcode

  • facebook

    twitter

  • Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.
해당 아이템을 이메일로 공유하기 원하시면 인증을 거치시기 바랍니다.

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse