title: Regulation of the human ABCB10 gene by E2F transcription factors.
abstract: Here, we report for the first time a functional study of transcriptional regulation of the human ABCB10 gene. We cloned a functional promoter sequence, and then showed that E2F2, E2F3 and E2F4 can activate transcription from the ABCB10 promoter. We identified sites responsible for this activation and confirmed direct binding of E2F4 to these sites in EMSA and ChIP assays. Finally, by silencing the expression of E2F factors we demonstrated their importance in maintenance of the basal ABCB10 expression. This study provides important atypical examples of E2F4 being a transcriptional activator rather than repressor as well as directly binding to a promoter and regulating it through an alternative and classical DNA consensus response element sequences. It also provides a mechanistic link between E2F4 and ABCB10, both of which are involved in the same physiological phenomena: erythroid lineage differentiation and maturation as well as protection against cardiomyocyte cell death.
authors.affiliation: Laboratory of Transcriptional Regulation, Institute of Medical Biology, Polish Academy of Sciences, Poland.
authors.forename: Iwona
authors.initials: I
authors.lastname: Karwaciak
authors.affiliation: Laboratory of Transcriptional Regulation, Institute of Medical Biology, Polish Academy of Sciences, Poland.
authors.forename: Lukasz
authors.initials: L
authors.lastname: Pulaski
authors.affiliation: Laboratory of Transcriptional Regulation, Institute of Medical Biology, Polish Academy of Sciences, Poland. Electronic address: mratajewski@cbm.pan.pl.
authors.forename: Marcin
authors.initials: M
authors.lastname: Ratajewski
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D050684:E2F Transcription Factors / Q000378:metabolism*; D057809:HEK293 Cells; D056945:Hep G2 Cells; D006801:Humans; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D015533:Transcriptional Activation
chemical_list: C412459:ABCB10 protein, human; D018528:ATP-Binding Cassette Transporters; D050684:E2F Transcription Factors
keywords: ABCB10; E2F; Mitochondrial ABC transporters; Promoter; Transcriptional regulation