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An Autoregulatory Pathway Establishes the Definitive Chromatin Conformation at the Pit-1 Locus.
- Source :
-
Molecular & Cellular Biology . May2015, Vol. 35 Issue 9, p1523-1532. 10p. - Publication Year :
- 2015
-
Abstract
- The transcription factor Pit-1 (POU1-F1) plays a dominant role in cell lineage expansion and differentiation in the anterior pituitary. Prior studies of the mouse Pit-1 (mPit-1) gene revealed that this master regulatory locus is activated at embryonic day 13.5 (E13.5) by an early enhancer (EE), whereas its subsequent expression throughout adult life is maintained by a more distal definitive enhancer (DE). Here, we demonstrate that the sequential actions of these two enhancers are linked to corresponding shifts in their proximities to the Pit-1 promoter. We further demonstrate that the looping of the definitive enhancer to the mPit-1 promoter is critically dependent on a self-sustaining autoregulatory mechanism mediated by the Pit-1 protein. These Pit-1-dependent actions are accompanied by localized recruitment of CBP and enrichment for H3K27 acetylation within the Pit-1 locus. These data support a model in which the sequential actions of two developmentally activated enhancers are linked to a corresponding shift in higher-order chromatin structures. This shift establishes an autoregulatory circuit that maintains durable expression of Pit-1 throughout adult life. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 02707306
- Volume :
- 35
- Issue :
- 9
- Database :
- Academic Search Index
- Journal :
- Molecular & Cellular Biology
- Publication Type :
- Academic Journal
- Accession number :
- 103564744
- Full Text :
- https://doi.org/10.1128/MCB.01283-14