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Multiple roles and regulatory mechanisms of the transcription factor HNF4 in the intestine

Hepatocyte nuclear factor 4-alpha (HNF4α) drives a complex array of transcriptional programs across multiple organs. Beyond its previously documented function in the liver, HNF4α has crucial roles in the kidney, intestine, and pancreas. In the intestine, a multitude of functions have been attributed...

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Autores principales: Vemuri, Kiranmayi, Radi, Sarah H., Sladek, Frances M., Verzi, Michael P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10450339/
https://www.ncbi.nlm.nih.gov/pubmed/37635981
http://dx.doi.org/10.3389/fendo.2023.1232569
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author Vemuri, Kiranmayi
Radi, Sarah H.
Sladek, Frances M.
Verzi, Michael P.
author_facet Vemuri, Kiranmayi
Radi, Sarah H.
Sladek, Frances M.
Verzi, Michael P.
author_sort Vemuri, Kiranmayi
collection PubMed
description Hepatocyte nuclear factor 4-alpha (HNF4α) drives a complex array of transcriptional programs across multiple organs. Beyond its previously documented function in the liver, HNF4α has crucial roles in the kidney, intestine, and pancreas. In the intestine, a multitude of functions have been attributed to HNF4 and its accessory transcription factors, including but not limited to, intestinal maturation, differentiation, regeneration, and stem cell renewal. Functional redundancy between HNF4α and its intestine-restricted paralog HNF4γ, and co-regulation with other transcription factors drive these functions. Dysregulated expression of HNF4 results in a wide range of disease manifestations, including the development of a chronic inflammatory state in the intestine. In this review, we focus on the multiple molecular mechanisms of HNF4 in the intestine and explore translational opportunities. We aim to introduce new perspectives in understanding intestinal genetics and the complexity of gastrointestinal disorders through the lens of HNF4 transcription factors.
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spelling pubmed-104503392023-08-26 Multiple roles and regulatory mechanisms of the transcription factor HNF4 in the intestine Vemuri, Kiranmayi Radi, Sarah H. Sladek, Frances M. Verzi, Michael P. Front Endocrinol (Lausanne) Endocrinology Hepatocyte nuclear factor 4-alpha (HNF4α) drives a complex array of transcriptional programs across multiple organs. Beyond its previously documented function in the liver, HNF4α has crucial roles in the kidney, intestine, and pancreas. In the intestine, a multitude of functions have been attributed to HNF4 and its accessory transcription factors, including but not limited to, intestinal maturation, differentiation, regeneration, and stem cell renewal. Functional redundancy between HNF4α and its intestine-restricted paralog HNF4γ, and co-regulation with other transcription factors drive these functions. Dysregulated expression of HNF4 results in a wide range of disease manifestations, including the development of a chronic inflammatory state in the intestine. In this review, we focus on the multiple molecular mechanisms of HNF4 in the intestine and explore translational opportunities. We aim to introduce new perspectives in understanding intestinal genetics and the complexity of gastrointestinal disorders through the lens of HNF4 transcription factors. Frontiers Media S.A. 2023-08-10 /pmc/articles/PMC10450339/ /pubmed/37635981 http://dx.doi.org/10.3389/fendo.2023.1232569 Text en Copyright © 2023 Vemuri, Radi, Sladek and Verzi https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Endocrinology
Vemuri, Kiranmayi
Radi, Sarah H.
Sladek, Frances M.
Verzi, Michael P.
Multiple roles and regulatory mechanisms of the transcription factor HNF4 in the intestine
title Multiple roles and regulatory mechanisms of the transcription factor HNF4 in the intestine
title_full Multiple roles and regulatory mechanisms of the transcription factor HNF4 in the intestine
title_fullStr Multiple roles and regulatory mechanisms of the transcription factor HNF4 in the intestine
title_full_unstemmed Multiple roles and regulatory mechanisms of the transcription factor HNF4 in the intestine
title_short Multiple roles and regulatory mechanisms of the transcription factor HNF4 in the intestine
title_sort multiple roles and regulatory mechanisms of the transcription factor hnf4 in the intestine
topic Endocrinology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10450339/
https://www.ncbi.nlm.nih.gov/pubmed/37635981
http://dx.doi.org/10.3389/fendo.2023.1232569
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