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


Journal

Endocrinology
ISSN: 1945-7170
Titre abrégé: Endocrinology
Pays: United States
ID NLM: 0375040

Informations de publication

Date de publication:
01 04 2021
Historique:
received: 26 11 2020
pubmed: 4 1 2021
medline: 21 10 2021
entrez: 3 1 2021
Statut: ppublish

Résumé

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.

Identifiants

pubmed: 33388754
pii: 6060060
doi: 10.1210/endocr/bqaa249
pmc: PMC7871365
pii:
doi:

Substances chimiques

Transcription Factor Pit-1 0
Prolactin 9002-62-4

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/K003097/1
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 091688
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 091688
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/F01760X/1
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/K015885/1
Pays : United Kingdom

Informations de copyright

© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society.

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Auteurs

Anne V McNamara (AV)

Systems Microscopy Centre, Division of Molecular and Cellular Function, School of Biological Sciences, Faculty Biology, Medicine & Health, Manchester Academic Health Sciences Centre, University of Manchester, Manchester, UK.

Raheela Awais (R)

School of Life Sciences, University of Liverpool, Liverpool, UK.

Hiroshi Momiji (H)

Mathematics Institute & Zeeman Institute for Systems Biology, and Infectious Epidemiology Research, University of Warwick, Senate House Coventry, UK.

Lee Dunham (L)

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

Karen Featherstone (K)

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

Claire V Harper (CV)

Department of Biology, Edge Hill University, Ormskirk, Lancashire, UK.

Antony A Adamson (AA)

Genome Editing Unit, Faculty of Biology, Medicine & Health, Manchester Academic Health Sciences Centre, University of Manchester, Manchester, UK.

Sabrina Semprini (S)

University/BHF Centre for Cardiovascular Science, The Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK.

Nicholas A Jones (NA)

Systems Microscopy Centre, Division of Molecular and Cellular Function, School of Biological Sciences, Faculty Biology, Medicine & Health, Manchester Academic Health Sciences Centre, University of Manchester, Manchester, UK.

David G Spiller (DG)

Systems Microscopy Centre, Division of Molecular and Cellular Function, School of Biological Sciences, Faculty Biology, Medicine & Health, Manchester Academic Health Sciences Centre, University of Manchester, Manchester, UK.

John J Mullins (JJ)

University/BHF Centre for Cardiovascular Science, The Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK.

Bärbel F Finkenstädt (BF)

Mathematics Institute & Zeeman Institute for Systems Biology, and Infectious Epidemiology Research, University of Warwick, Senate House Coventry, UK.

David Rand (D)

Mathematics Institute & Zeeman Institute for Systems Biology, and Infectious Epidemiology Research, University of Warwick, Senate House Coventry, UK.

Michael R H White (MRH)

Systems Microscopy Centre, Division of Molecular and Cellular Function, School of Biological Sciences, Faculty Biology, Medicine & Health, Manchester Academic Health Sciences Centre, University of Manchester, Manchester, UK.

Julian R E Davis (JRE)

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

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Classifications MeSH