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Transcription Factor Pit-1 Affects Transcriptional Timing in the Dual-Promoter Human Prolactin Gene. | LitMetric

Transcription Factor Pit-1 Affects Transcriptional Timing in the Dual-Promoter Human Prolactin Gene.

Endocrinology

Division of Diabetes, Endocrinology & Gastroenterology, School of Medical Sciences, Faculty of Biology, Medicine & Health, Manchester Academic Health Sciences Centre, University of Manchester, Manchester, UK.

Published: April 2021

AI Article Synopsis

  • Gene transcription occurs in bursts with silent periods, influenced by promoter structure; this study focuses on the human prolactin (hPRL) gene with two promoters.
  • The study found that the pituitary-specific promoter, requiring the transcription factor Pit-1, generates longer and more intense transcriptional bursts compared to the nonpituitary alternate promoter.
  • Results from mathematical modeling and knockdown experiments showed that Pit-1 not only stabilizes transcription bursts but also regulates the timing of these transcription cycles, enhancing its role beyond cell specificity.

Article Abstract

Gene transcription occurs in short bursts interspersed with silent periods, and these kinetics can be altered by promoter structure. The effect of alternate promoter architecture on transcription bursting is not known. We studied the human prolactin (hPRL) gene that contains 2 promoters, a pituitary-specific promoter that requires the transcription factor Pit-1 and displays dramatic transcriptional bursting activity and an alternate upstream promoter that is active in nonpituitary tissues. We studied large hPRL genomic fragments with luciferase reporters, and used bacterial artificial chromosome recombineering to manipulate critical promoter regions. Stochastic switch mathematical modelling of single-cell time-lapse luminescence image data revealed that the Pit-1-dependent promoter showed longer, higher-amplitude transcriptional bursts. Knockdown studies confirmed that the presence of Pit-1 stabilized and prolonged periods of active transcription. Pit-1 therefore plays an active role in establishing the timing of transcription cycles, in addition to its cell-specific functions.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7871365PMC
http://dx.doi.org/10.1210/endocr/bqaa249DOI Listing

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