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The Transcriptional Co-Regulator HCF-1 Is Required for INS-1 β-cell Glucose-Stimulated Insulin Secretion
The transcriptional co-regulator host cell factor-1 (HCF-1) plays critical roles in promoting cell cycle progression in diverse cell types, and in maintaining self-renewal of embryonic stem cells, but its role in pancreatic β-cell function has not been investigated. Immunhistochemistry of mouse panc...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3826731/ https://www.ncbi.nlm.nih.gov/pubmed/24250814 http://dx.doi.org/10.1371/journal.pone.0078841 |
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author | Iwata, Terri N. Cowley, Timothy J. Sloma, Michael Ji, Yewei Kim, Hana Qi, Ling Lee, Siu Sylvia |
author_facet | Iwata, Terri N. Cowley, Timothy J. Sloma, Michael Ji, Yewei Kim, Hana Qi, Ling Lee, Siu Sylvia |
author_sort | Iwata, Terri N. |
collection | PubMed |
description | The transcriptional co-regulator host cell factor-1 (HCF-1) plays critical roles in promoting cell cycle progression in diverse cell types, and in maintaining self-renewal of embryonic stem cells, but its role in pancreatic β-cell function has not been investigated. Immunhistochemistry of mouse pancreas revealed nuclear expression of HCF-1 in pancreatic islets. Reducing HCF-1 expression in the INS-1 pancreatic β-cell line resulted in reduced cell proliferation, reduced glucose-stimulated insulin secretion, and reduced expression of the critical β-cell transcription factor Pdx1. HCF-1 is a known co-activator of the E2F1 transcription factor, and loss of E2F1 results in pancreatic β-cell dysfunction and reduced expression of Pdx1. Therefore we wondered whether HCF-1 might be required for E2F1 regulation of Pdx1. Chromatin immunoprecipitation experiments revealed that HCF-1 and E2F1 co-localize to the Pdx1 promoter. These results indicate that HCF-1 represents a novel transcriptional regulator required for maintaining pancreatic β-cell function. |
format | Online Article Text |
id | pubmed-3826731 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-38267312013-11-18 The Transcriptional Co-Regulator HCF-1 Is Required for INS-1 β-cell Glucose-Stimulated Insulin Secretion Iwata, Terri N. Cowley, Timothy J. Sloma, Michael Ji, Yewei Kim, Hana Qi, Ling Lee, Siu Sylvia PLoS One Research Article The transcriptional co-regulator host cell factor-1 (HCF-1) plays critical roles in promoting cell cycle progression in diverse cell types, and in maintaining self-renewal of embryonic stem cells, but its role in pancreatic β-cell function has not been investigated. Immunhistochemistry of mouse pancreas revealed nuclear expression of HCF-1 in pancreatic islets. Reducing HCF-1 expression in the INS-1 pancreatic β-cell line resulted in reduced cell proliferation, reduced glucose-stimulated insulin secretion, and reduced expression of the critical β-cell transcription factor Pdx1. HCF-1 is a known co-activator of the E2F1 transcription factor, and loss of E2F1 results in pancreatic β-cell dysfunction and reduced expression of Pdx1. Therefore we wondered whether HCF-1 might be required for E2F1 regulation of Pdx1. Chromatin immunoprecipitation experiments revealed that HCF-1 and E2F1 co-localize to the Pdx1 promoter. These results indicate that HCF-1 represents a novel transcriptional regulator required for maintaining pancreatic β-cell function. Public Library of Science 2013-11-08 /pmc/articles/PMC3826731/ /pubmed/24250814 http://dx.doi.org/10.1371/journal.pone.0078841 Text en © 2013 Iwata et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Iwata, Terri N. Cowley, Timothy J. Sloma, Michael Ji, Yewei Kim, Hana Qi, Ling Lee, Siu Sylvia The Transcriptional Co-Regulator HCF-1 Is Required for INS-1 β-cell Glucose-Stimulated Insulin Secretion |
title | The Transcriptional Co-Regulator HCF-1 Is Required for INS-1 β-cell Glucose-Stimulated Insulin Secretion |
title_full | The Transcriptional Co-Regulator HCF-1 Is Required for INS-1 β-cell Glucose-Stimulated Insulin Secretion |
title_fullStr | The Transcriptional Co-Regulator HCF-1 Is Required for INS-1 β-cell Glucose-Stimulated Insulin Secretion |
title_full_unstemmed | The Transcriptional Co-Regulator HCF-1 Is Required for INS-1 β-cell Glucose-Stimulated Insulin Secretion |
title_short | The Transcriptional Co-Regulator HCF-1 Is Required for INS-1 β-cell Glucose-Stimulated Insulin Secretion |
title_sort | transcriptional co-regulator hcf-1 is required for ins-1 β-cell glucose-stimulated insulin secretion |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3826731/ https://www.ncbi.nlm.nih.gov/pubmed/24250814 http://dx.doi.org/10.1371/journal.pone.0078841 |
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