Cargando…

Forkhead Box Transcription Factors of the FOXA Class Are Required for Basal Transcription of Angiotensin-Converting Enzyme 2

Angiotensin-converting enzyme 2 (ACE2) has protective effects on a wide range of morbidities associated with elevated angiotensin-II signaling. Most tissues, including pancreatic islets, express ACE2 mainly from the proximal promoter region. We previously found that hepatocyte nuclear factors 1α and...

Descripción completa

Detalles Bibliográficos
Autores principales: Pedersen, Kim Brint, Chodavarapu, Harshita, Lazartigues, Eric
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Endocrine Society 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5656262/
https://www.ncbi.nlm.nih.gov/pubmed/29082356
http://dx.doi.org/10.1210/js.2016-1071
_version_ 1783273678478245888
author Pedersen, Kim Brint
Chodavarapu, Harshita
Lazartigues, Eric
author_facet Pedersen, Kim Brint
Chodavarapu, Harshita
Lazartigues, Eric
author_sort Pedersen, Kim Brint
collection PubMed
description Angiotensin-converting enzyme 2 (ACE2) has protective effects on a wide range of morbidities associated with elevated angiotensin-II signaling. Most tissues, including pancreatic islets, express ACE2 mainly from the proximal promoter region. We previously found that hepatocyte nuclear factors 1α and 1β stimulate ACE2 expression from three highly conserved hepatocyte nuclear factor 1 binding motifs in the proximal promoter region. We hypothesized that other highly conserved motifs would also affect ACE2 expression. By systematic mutation of conserved elements, we identified five regions affecting ACE2 expression, of which two regions bound transcriptional activators. One of these is a functional FOXA binding motif. We further identified the main protein binding the FOXA motif in 832/13 insulinoma cells as well as in mouse pancreatic islets as FOXA2.
format Online
Article
Text
id pubmed-5656262
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher Endocrine Society
record_format MEDLINE/PubMed
spelling pubmed-56562622017-12-20 Forkhead Box Transcription Factors of the FOXA Class Are Required for Basal Transcription of Angiotensin-Converting Enzyme 2 Pedersen, Kim Brint Chodavarapu, Harshita Lazartigues, Eric J Endocr Soc Research Articles Angiotensin-converting enzyme 2 (ACE2) has protective effects on a wide range of morbidities associated with elevated angiotensin-II signaling. Most tissues, including pancreatic islets, express ACE2 mainly from the proximal promoter region. We previously found that hepatocyte nuclear factors 1α and 1β stimulate ACE2 expression from three highly conserved hepatocyte nuclear factor 1 binding motifs in the proximal promoter region. We hypothesized that other highly conserved motifs would also affect ACE2 expression. By systematic mutation of conserved elements, we identified five regions affecting ACE2 expression, of which two regions bound transcriptional activators. One of these is a functional FOXA binding motif. We further identified the main protein binding the FOXA motif in 832/13 insulinoma cells as well as in mouse pancreatic islets as FOXA2. Endocrine Society 2017-03-06 /pmc/articles/PMC5656262/ /pubmed/29082356 http://dx.doi.org/10.1210/js.2016-1071 Text en Copyright © 2017 Endocrine Society https://creativecommons.org/licenses/by-nc-nd/4.0/ This article is published under the terms of the Creative Commons Attribution-Non Commercial License (CC BY-NC-ND; https://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Research Articles
Pedersen, Kim Brint
Chodavarapu, Harshita
Lazartigues, Eric
Forkhead Box Transcription Factors of the FOXA Class Are Required for Basal Transcription of Angiotensin-Converting Enzyme 2
title Forkhead Box Transcription Factors of the FOXA Class Are Required for Basal Transcription of Angiotensin-Converting Enzyme 2
title_full Forkhead Box Transcription Factors of the FOXA Class Are Required for Basal Transcription of Angiotensin-Converting Enzyme 2
title_fullStr Forkhead Box Transcription Factors of the FOXA Class Are Required for Basal Transcription of Angiotensin-Converting Enzyme 2
title_full_unstemmed Forkhead Box Transcription Factors of the FOXA Class Are Required for Basal Transcription of Angiotensin-Converting Enzyme 2
title_short Forkhead Box Transcription Factors of the FOXA Class Are Required for Basal Transcription of Angiotensin-Converting Enzyme 2
title_sort forkhead box transcription factors of the foxa class are required for basal transcription of angiotensin-converting enzyme 2
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5656262/
https://www.ncbi.nlm.nih.gov/pubmed/29082356
http://dx.doi.org/10.1210/js.2016-1071
work_keys_str_mv AT pedersenkimbrint forkheadboxtranscriptionfactorsofthefoxaclassarerequiredforbasaltranscriptionofangiotensinconvertingenzyme2
AT chodavarapuharshita forkheadboxtranscriptionfactorsofthefoxaclassarerequiredforbasaltranscriptionofangiotensinconvertingenzyme2
AT lazartigueseric forkheadboxtranscriptionfactorsofthefoxaclassarerequiredforbasaltranscriptionofangiotensinconvertingenzyme2