Role of Meis1 in the Transcription of Mitochondrial Genes.
Miki Tomoeda, Yu-Fen Jin, Michiko Yuki, Chiaki Kubo, Hidenori Yoshizawa, Yasuko Nishizawa, Yasuhiko Tomita. Kobe International College, Hyogo, Japan; Osaka Medical Center for Cancer and Cardiovascular Diseases, Japan
Background: Our previous studies showed that Hox cofactors (Pre B cell transcription factors: PBXs and Myeloid ectopic viral integration sites: MEISs) as important transcription factor of Valosin-containing protein (VCP). To elucidate difference of function among PBXs and MEISs as transcription factors, cDNA microarray analysis was performed using siRNA transfected pancreatic cancer cell line Panc-1. The result showed down-regulation with MEIS1 siRNA-transfection and upregulation with PBX1, and PBX2-transfection of mitochondrial genes.
Design: Luciferase reporter constructs containing serially deleted transcription initiation site of mtDNA were transfected into Panc-1. The deletion and mutation at the binding motifs of MEIS1 was introduced. Chromatin immunoprecipitation assay was carried out to find the binding of MEIS1 to the transcription initiation site of mtDNA. MEIS1 siRNA was transiently transfected to Panc1, and expression of mitochondrial genes was analyzed by cDNA microarray and quantitative PCR. Deletion of mitochondrial membrane potential was observed by fluorescence microscopic examination with JC-1.
Results: The deletion and mutation at the binding motif of MEIS1 reduced the luciferase activity, indicating that the MEIS1 motif mediated the transactivation of mitochondrial gene. Chromatin immunoprecipitation assay showed the binding of MEIS1 to the transcription initiation site of mtDNA. The knockdown of MEIS1 by siRNA decreased the expression level of mitochondrial genes and mitochondrial membrane potential.
Conclusions: These findings indicate that MEIS1 plays a crucial role in mitochondrial gene expression.
Wednesday, March 2, 2011 9:30 AM
Poster Session V # 242, Wednesday Morning