A Single cis Element Maintains Repression of the Key Developmental Regulator Gata2

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A Single cis Element Maintains Repression of the Key Developmental Regulator Gata2

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Title: A Single cis Element Maintains Repression of the Key Developmental Regulator Gata2
Author: Snow, Jonathan W.; Fujiwara, Tohru; Emambokus, Nikla E.; Grass, Jeffrey A.; Bresnick, Emery H.; Orkin, Stuart Holland; Trowbridge, Jennifer J.

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Citation: Snow, Jonathan W., Jennifer J. Trowbridge, Tohru Fujiwara, Nikla E. Emambokus, Jeffrey A. Grass, Stuart H. Orkin, and Emery H. Bresnick. 2010. A Single cis element maintains repression of the key developmental regulator Gata2. PLoS Genetics 6(9): e1001103.
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Abstract: In development, lineage-restricted transcription factors simultaneously promote differentiation while repressing alternative fates. Molecular dissection of this process has been challenging as transcription factor loci are regulated by many trans-acting factors functioning through dispersed cis elements. It is not understood whether these elements function collectively to confer transcriptional regulation, or individually to control specific aspects of activation or repression, such as initiation versus maintenance. Here, we have analyzed cis element regulation of the critical hematopoietic factor Gata2, which is expressed in early precursors and repressed as GATA-1 levels rise during terminal differentiation. We engineered mice lacking a single cis element −1.8 kb upstream of the Gata2 transcriptional start site. Although Gata2 is normally repressed in late-stage erythroblasts, the −1.8 kb mutation unexpectedly resulted in reactivated Gata2 transcription, blocked differentiation, and an aberrant lineage-specific gene expression pattern. Our findings demonstrate that the −1.8 kb site selectively maintains repression, confers a specific histone modification pattern and expels RNA Polymerase II from the locus. These studies reveal how an individual cis element establishes a normal developmental program via regulating specific steps in the mechanism by which a critical transcription factor is repressed.
Published Version: doi:10.1371/journal.pgen.1001103
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2936534/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:4739299
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