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oai:repisalud.isciii.es:20.500.12105/64972025-04-01T12:14:18Zcom_20.500.12105_2052com_20.500.12105_2051com_20.500.12105_19604col_20.500.12105_19609col_20.500.12105_19605

00925njm 22002777a 4500 dc Alvaro-Blanco, Josué author Urso, Katia author Chiodo, Yuri author Martin-Cortazar, Carla author Kourani, Omar author Gomez-del Arco, Pablo author Rodriguez-Martinez, Maria author Calonge, Esther author Alcamí, José author Redondo, Juan Miguel author Iglesias, Teresa author Campanero, Miguel R author 2017 Most E2F-binding sites repress transcription through the recruitment of Retinoblastoma (RB) family members until the end of the G1 cell-cycle phase. Although the MYB promoter contains an E2F-binding site, its transcription is activated shortly after the exit from quiescence, before RB family members inactivation, by unknown mechanisms. We had previously uncovered a nuclear factor distinct from E2F, Mybsp, whose DNA-binding site overlapped the E2F element and had hypothesized that this factor might overcome the transcriptional repression of MYB by E2F-RB family members. We have purified Myb-sp and discovered that Myc-associated zinc finger proteins (MAZ) are major components. We show that various MAZ isoforms are present in Myb-sp and activate transcription via the MYB-E2F element. Moreover, while forced RB or p130 expression repressed the activity of a luciferase reporter driven by the MYB-E2F element, co-expression of MAZ proteins not only reverted repression, but also activated transcription. Finally, we show that MAZ binds the MYB promoter in vivo, that its binding site is critical for MYB transactivation, and that MAZ knockdown inhibits MYB expression during the exit from quiescence. Together, these data indicate that MAZ is essential to bypass MYB promoter repression by RB family members and to induce MYB expression. Nucleic Acids Res. 2017; 45(17):9960-9975 10.1093/nar/gkx641 1362-4962 0305-1048 Nucleic Acids Research 28973440 http://hdl.handle.net/20.500.12105/6497 ZINC-FINGER PROTEIN CELL-CYCLE CONTROL C-MYB TRANSCRIPTION FACTORS BINDING-SITES NEGATIVE REGULATION SIGNALING PATHWAY GENE-EXPRESSION SPLICE VARIANT RECEPTOR GENE MAZ induces MYB expression during the exit from quiescence via the E2F site in the MYB promoter