التفاصيل البيبلوغرافية
| العنوان: |
An Autoregulatory Pathway Establishes the Definitive Chromatin Conformation at the Pit-1 Locus. |
| المؤلفون: |
Yugong Ho1 yho@mail.med.upenn.edu, Cooke, Nancy E.1,2, Liebhaber, Stephen A.1,2 |
| المصدر: |
Molecular & Cellular Biology. May2015, Vol. 35 Issue 9, p1523-1532. 10p. |
| مصطلحات موضوعية: |
*CHROMATIN, *CHROMOSOMES, *TRANSCRIPTION factors, *FATE mapping (Genetics), *DEVELOPMENTAL biology |
| مستخلص: |
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] |
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