title: The transcriptional co-regulator HCF-1 is required for INS-1 β-cell glucose-stimulated insulin secretion.
abstract: 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.
authors.affiliation: Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York, United States of America.
authors.forename: Terri N
authors.initials: TN
authors.lastname: Iwata
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Cowley
authors.forename: Michael
authors.initials: M
authors.lastname: Sloma
authors.forename: Yewei
authors.initials: Y
authors.lastname: Ji
authors.forename: Hana
authors.initials: H
authors.lastname: Kim
authors.forename: Ling
authors.initials: L
authors.lastname: Qi
authors.forename: Siu Sylvia
authors.initials: SS
authors.lastname: Lee
mesh_terms: D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation / Q000235:genetics; D002843:Chromatin / Q000235:genetics / Q000378:metabolism; D050687:E2F1 Transcription Factor / Q000235:genetics; D005786:Gene Expression Regulation; D005947:Glucose / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics; D051863:Host Cell Factor C1 / Q000235:genetics* / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D007515:Islets of Langerhans / Q000378:metabolism*; D051379:Mice; D011401:Promoter Regions, Genetic; D051381:Rats; D015534:Trans-Activators / Q000235:genetics
chemical_list: D002843:Chromatin; D050687:E2F1 Transcription Factor; C497693:Hcfc1 protein, mouse; D018398:Homeodomain Proteins; D051863:Host Cell Factor C1; D007328:Insulin; D015534:Trans-Activators; C084010:pancreatic and duodenal homeobox 1 protein; D005947:Glucose