期刊
BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS
卷 1829, 期 10, 页码 1136-1146出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbagrm.2013.07.006
关键词
DREF; Drosophila; Nuclear DNA replication; Mitochondrial biogenesis; Transcriptional regulation
资金
- Center for Biomedical Research on Rare Diseases (CIBERER) [INTRA/08/743.2]
- Instituto de Salud Carlos III [PI 07/0167, PI 10/0703]
- Comunidad de Madrid [GEN-0269/2006, MITOLAB S2010/BMD-2402]
- Universita di Bari, Progetto di Ricerca di Ateneo
- National Institutes of Health [GM45295]
DREF [DRE (DNA replication-related element)-binding factor] controls the transcription of numerous genes in Drosophila, many involved in nuclear DNA (nDNA) replication and cell proliferation, three in mitochondrial DNA (mtDNA) replication and two in mtDNA transcription termination. In this work, we have analysed the involvement of DREF in the expression of the known remaining genes engaged in the minimal mtDNA replication (d-mtDNA helicase) and transcription (the activator d-mtTFB2) machineries and of a gene involved in mitochondrial mRNA translation (d-mtTFB1). We have identified their transcriptional initiation sites and DRE sequences in their promoter regions. Gel-shift and chromatin immunoprecipitation assays demonstrate that DREF interacts in vitro and in vivo with the d-mtDNA helicase and d-mtTFB2, but not with the d-mtTFB1 promoters. Transient transfection assays in Drosophila S2 cells with mutated DRE motifs and truncated promoter regions show that DREF controls the transcription of d-mtDNA helicase and d-mtTFB2, but not that of d-mtTFB1. RNA interference of DREF in S2 cells reinforces these results showing a decrease in the mRNA levels of d-mtDNA helicase and d-mtTFB2 and no changes in those of the d-mtTFB1. These results link the genetic regulation of nuclear DNA replication with the genetic control of mtDNA replication and transcriptional activation in Drosophila. (C) 2013 Elsevier B.V. All rights reserved.
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