title: ISL-1 promotes pancreatic islet cell proliferation by forming an ISL-1/Set7/9/PDX-1 complex.
abstract: Islet-1 (ISL-1), a LIM-homeodomain transcription factor, has been recently found to be essential for promoting postnatal pancreatic islet proliferation. However, the detailed mechanism has not yet been elucidated. In the present study, we investigated the mechanism by which ISL-1 promotes β-cell proliferation through regulation of CyclinD1 in HIT-T15 and NIT-1 cells, as well in rat islet mass. Our results provide the evidence that ISL-1 promotes adult pancreatic islet β-cell proliferation by activating CyclinD1 transcription through cooperation with Set7/9 and PDX-1 to form an ISL-1/Set7/9/PDX-1 complex. This complex functions in an ISL-1-dependent manner, with Set7/9 functioning not only as a histone methyltransferase, which increases the histone H3K4 tri-methylation of the CyclinD1 promoter region, but also an adaptor to bridge ISL-1 and PDX-1, while PDX-1 functions as a RNA pol II binding modulator. Furthermore, the formation of the ISL-1/Set7/9/PDX-1 complex is positively associated with insulin-like growth factor-1 treatment in NIT and HIT-T15 cells in vitro, while may be negatively correlated with age in vivo.
authors.affiliation: a Department of Biochemistry and Molecular Biology ; School of Basic Medical Sciences; Key Laboratory of Molecular Cardiovascular Sciences; Ministry of Education of China; Peking University ; Beijing , China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Yang
authors.affiliation: a Department of Biochemistry and Molecular Biology ; School of Basic Medical Sciences; Key Laboratory of Molecular Cardiovascular Sciences; Ministry of Education of China; Peking University ; Beijing , China.|b Current address: Department of Biochemistry and Molecular Biology ; School of Basic Medical Sciences; Kunming Medical University ; Kunming , China.
authors.forename: Qiao
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: a Department of Biochemistry and Molecular Biology ; School of Basic Medical Sciences; Key Laboratory of Molecular Cardiovascular Sciences; Ministry of Education of China; Peking University ; Beijing , China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Lu
authors.affiliation: a Department of Biochemistry and Molecular Biology ; School of Basic Medical Sciences; Key Laboratory of Molecular Cardiovascular Sciences; Ministry of Education of China; Peking University ; Beijing , China.
authors.forename: Zhuqing
authors.initials: Z
authors.lastname: Jia
authors.affiliation: a Department of Biochemistry and Molecular Biology ; School of Basic Medical Sciences; Key Laboratory of Molecular Cardiovascular Sciences; Ministry of Education of China; Peking University ; Beijing , China.
authors.forename: Ping
authors.initials: P
authors.lastname: Chen
authors.affiliation: a Department of Biochemistry and Molecular Biology ; School of Basic Medical Sciences; Key Laboratory of Molecular Cardiovascular Sciences; Ministry of Education of China; Peking University ; Beijing , China.
authors.forename: Kangtao
authors.initials: K
authors.lastname: Ma
authors.affiliation: a Department of Biochemistry and Molecular Biology ; School of Basic Medical Sciences; Key Laboratory of Molecular Cardiovascular Sciences; Ministry of Education of China; Peking University ; Beijing , China.
authors.forename: Weiping
authors.initials: W
authors.lastname: Wang
authors.affiliation: a Department of Biochemistry and Molecular Biology ; School of Basic Medical Sciences; Key Laboratory of Molecular Cardiovascular Sciences; Ministry of Education of China; Peking University ; Beijing , China.
authors.forename: Chunyan
authors.initials: C
authors.lastname: Zhou
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000235:genetics / Q000502:physiology; D006224:Cricetinae; D019938:Cyclin D1 / Q000235:genetics*; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D050417:Insulin-Secreting Cells / Q000166:cytology*; D060850:LIM-Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D051381:Rats; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D018398:Homeodomain Proteins; D060850:LIM-Homeodomain Proteins; D015534:Trans-Activators; D014157:Transcription Factors; C063843:insulin gene enhancer binding protein Isl-1; C084010:pancreatic and duodenal homeobox 1 protein; D019938:Cyclin D1; D011495:Histone-Lysine N-Methyltransferase; C540312:SETD7 protein, human
keywords: ISL-1; PDX-1; Set7/9; pancreatic islets; proliferation