PMID- 21278380 OWN - NLM STAT- MEDLINE DCOM- 20110609 LR - 20211020 IS - 1083-351X (Electronic) IS - 0021-9258 (Print) IS - 0021-9258 (Linking) VI - 286 IP - 12 DP - 2011 Mar 25 TI - ATF2 interacts with beta-cell-enriched transcription factors, MafA, Pdx1, and beta2, and activates insulin gene transcription. PG - 10449-56 LID - 10.1074/jbc.M110.209510 [doi] AB - Pancreatic beta-cell-restricted expression of insulin is established through several critical cis-regulatory elements located in the insulin gene promoter region. The principal cis elements are A-boxes, E1, and C1/RIPE3b. The beta-cell-enriched transcription factors Pdx1 and Beta2 bind to the A-boxes and E1 element, respectively. A beta-cell-specific trans-acting factor binding to C1/RIPE3b (termed RIPE3b1 activator) was detected by electrophoretic mobility shift assay and has been identified as MafA, a member of the Maf family of basic leucine zipper (bZip) proteins. Here, ATF2, a member of the ATF/CREB family of basic leucine zipper proteins, was identified as a component of the RIPE3b1 activator. ATF2 alone was unable to bind to the C1/RIPE3b element but acquired binding capacity upon complex formation with MafA. ATF2 also interacted with Pdx1 and Beta2, and co-expression of ATF2, MafA, Pdx1, and Beta2 resulted in a synergistic activation of the insulin promoter. Immunohistochemical analysis of mouse pancreas tissue sections showed that ATF2 is enriched in islet endocrine cells, including beta-cells. RNAi-mediated knockdown of MafA or ATF2 in the MIN6 beta-cell line resulted in a significant decrease in endogenous levels of insulin mRNA. These data indicate that ATF2 is an essential component of the positive regulators of the insulin gene expression. FAU - Han, Song-iee AU - Han SI AD - Laboratory of Molecular and Developmental Biology, Graduate School of Biological Science, Nara Institute of Science and Technology, Ikoma 630-0192, Japan. FAU - Yasuda, Kunio AU - Yasuda K FAU - Kataoka, Kohsuke AU - Kataoka K LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20110128 PL - United States TA - J Biol Chem JT - The Journal of biological chemistry JID - 2985121R RN - 0 (ATF2 protein, human) RN - 0 (Activating Transcription Factor 2) RN - 0 (Atf2 protein, mouse) RN - 0 (Basic Helix-Loop-Helix Transcription Factors) RN - 0 (Homeodomain Proteins) RN - 0 (Insulin) RN - 0 (MAFA protein, human) RN - 0 (Maf Transcription Factors, Large) RN - 0 (Mafa protein, mouse) RN - 0 (NEUROD1 protein, human) RN - 0 (Neurod1 protein, mouse) RN - 0 (RNA, Messenger) RN - 0 (Trans-Activators) RN - 0 (pancreatic and duodenal homeobox 1 protein) SB - IM MH - Activating Transcription Factor 2/genetics/*metabolism MH - Animals MH - Basic Helix-Loop-Helix Transcription Factors/genetics/*metabolism MH - Gene Expression Regulation/physiology MH - Gene Knockdown Techniques MH - HeLa Cells MH - Homeodomain Proteins/genetics/*metabolism MH - Humans MH - Insulin/*biosynthesis/genetics MH - Insulin-Secreting Cells/cytology/*metabolism MH - Maf Transcription Factors, Large/genetics/*metabolism MH - Mice MH - NIH 3T3 Cells MH - Protein Binding MH - RNA, Messenger/biosynthesis/genetics MH - Response Elements/physiology MH - Trans-Activators/genetics/*metabolism MH - Transcription, Genetic/*physiology PMC - PMC3060498 EDAT- 2011/02/01 06:00 MHDA- 2011/06/10 06:00 PMCR- 2012/03/25 CRDT- 2011/02/01 06:00 PHST- 2011/02/01 06:00 [entrez] PHST- 2011/02/01 06:00 [pubmed] PHST- 2011/06/10 06:00 [medline] PHST- 2012/03/25 00:00 [pmc-release] AID - S0021-9258(20)53870-2 [pii] AID - M110.209510 [pii] AID - 10.1074/jbc.M110.209510 [doi] PST - ppublish SO - J Biol Chem. 2011 Mar 25;286(12):10449-56. doi: 10.1074/jbc.M110.209510. Epub 2011 Jan 28.