Abstract:
:Cis-regulatory modules (CRMs) are defined by unique combinations of transcription factor-binding sites. Emerging evidence suggests that the number, affinity, and organization of sites play important roles in regulating enhancer output and, ultimately, gene expression. Here, we investigate how the cis-regulatory logic of a tissue-specific CRM responsible for even-skipped (eve) induction during cardiogenesis organizes the competing inputs of two E-twenty-six (ETS) members: the activator Pointed (Pnt) and the repressor Yan. Using a combination of reporter gene assays and CRISPR-Cas9 gene editing, we suggest that Yan and Pnt have distinct syntax preferences. Not only does Yan prefer high-affinity sites, but an overlapping pair of such sites is necessary and sufficient for Yan to tune Eve expression levels in newly specified cardioblasts and block ectopic Eve induction and cell fate specification in surrounding progenitors. Mechanistically, the efficient Yan recruitment promoted by this high-affinity ETS supersite not only biases Yan-Pnt competition at the specific CRM but also organizes Yan-repressive complexes in three dimensions across the eve locus. Taken together, our results uncover a novel mechanism by which differential interpretation of CRM syntax by a competing repressor-activator pair can confer both specificity and robustness to developmental transitions.
journal_name
Genes Devjournal_title
Genes & developmentauthors
Boisclair Lachance JF,Webber JL,Hong L,Dinner AR,Rebay Idoi
10.1101/gad.307132.117subject
Has Abstractpub_date
2018-03-01 00:00:00pages
389-401issue
5-6eissn
0890-9369issn
1549-5477pii
gad.307132.117journal_volume
32pub_type
杂志文章abstract::Unrepaired DNA lesions in the template strand block the replication fork. In yeast, Mec1 protein kinase-mediated replication checkpoint prevents the breakdown of replication forks and maintains viability in DNA-damaged cells going through the S phase. By ensuring that the replisome does not dissociate from the fork st...
journal_title:Genes & development
pub_type: 杂志文章
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journal_title:Genes & development
pub_type: 杂志文章
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journal_title:Genes & development
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journal_title:Genes & development
pub_type: 杂志文章
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journal_title:Genes & development
pub_type: 杂志文章
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journal_title:Genes & development
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journal_title:Genes & development
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pub_type: 杂志文章
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pub_type: 杂志文章
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journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.377106
更新日期:2006-06-01 00:00:00
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journal_title:Genes & development
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journal_title:Genes & development
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journal_title:Genes & development
pub_type: 杂志文章
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更新日期:2003-06-15 00:00:00
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journal_title:Genes & development
pub_type: 杂志文章
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pub_type: 杂志文章
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journal_title:Genes & development
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journal_title:Genes & development
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journal_title:Genes & development
pub_type: 杂志文章
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更新日期:2001-07-01 00:00:00
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journal_title:Genes & development
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journal_title:Genes & development
pub_type: 杂志文章
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journal_title:Genes & development
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journal_title:Genes & development
pub_type: 杂志文章
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