RESUMEN
The endocycle represents an alternative cell cycle that is activated in various developmental processes, including placental formation, Drosophila oogenesis, and leaf development. In endocycling cells, mitotic cell cycle exit is followed by successive doublings of the DNA content, resulting in polyploidy. The timing of endocycle onset is crucial for correct development, because polyploidization is linked with cessation of cell division and initiation of terminal differentiation. The anaphase-promoting complex/cyclosome (APC/C) activator genes CDH1, FZR, and CCS52 are known to promote endocycle onset in human, Drosophila, and Medicago species cells, respectively; however, the genetic pathways governing development-dependent APC/C(CDH1/FZR/CCS52) activity remain unknown. We report that the atypical E2F transcription factor E2Fe/DEL1 controls the expression of the CDH1/FZR orthologous CCS52A2 gene from Arabidopsis thaliana. E2Fe/DEL1 misregulation resulted in untimely CCS52A2 transcription, affecting the timing of endocycle onset. Correspondingly, ectopic CCS52A2 expression drove cells into the endocycle prematurely. Dynamic simulation illustrated that E2Fe/DEL1 accounted for the onset of the endocycle by regulating the temporal expression of CCS52A2 during the cell cycle in a development-dependent manner. Analogously, the atypical mammalian E2F7 protein was associated with the promoter of the APC/C-activating CDH1 gene, indicating that the transcriptional control of APC/C activator genes by atypical E2Fs might be evolutionarily conserved.
Asunto(s)
Arabidopsis/citología , Arabidopsis/metabolismo , Ciclo Celular , Regulación de la Expresión Génica de las Plantas , Factores de Transcripción/metabolismo , Complejos de Ubiquitina-Proteína Ligasa/metabolismo , Ciclosoma-Complejo Promotor de la Anafase , Arabidopsis/genética , Arabidopsis/crecimiento & desarrollo , Evolución Molecular , Glucuronidasa/metabolismo , Mitosis , Hojas de la Planta/crecimiento & desarrollo , Plantas Modificadas Genéticamente , Regiones Promotoras Genéticas , Factores de Tiempo , Factores de Transcripción/genética , Complejos de Ubiquitina-Proteína Ligasa/genéticaRESUMEN
The Stress-responsive activator of p300 (Strap) is a transcription cofactor that has an important role in the control of DNA damage response through its ability to regulate p53 activity. Here, we report that Strap is inducible by heat shock and stimulates the transcription of heat-shock genes. A chromatin-associated complex involving heat-shock factor 1 (HSF1), Strap and the p300 coactivator assembles on the heat-shock protein 70 (hsp70) promoter, and Strap augments HSF1 binding and chromatin acetylation in Hsp genes, most probably through the p300 histone acetyltransferase. Cells depleted of Strap do not survive under heat-shock conditions. These results indicate that Strap is an essential cofactor that acts at the level of chromatin control to regulate heat-shock-responsive transcription.
Asunto(s)
Proteínas Portadoras/metabolismo , Respuesta al Choque Térmico , Factores de Transcripción/metabolismo , Acetilación , Línea Celular Tumoral , Supervivencia Celular , Cromatina/metabolismo , Proteínas de Unión al ADN/metabolismo , Regulación de la Expresión Génica , Proteínas HSP70 de Choque Térmico/genética , Proteínas HSP70 de Choque Térmico/metabolismo , Factores de Transcripción del Choque Térmico , Humanos , Regiones Promotoras Genéticas/genética , Unión Proteica , Factores de Transcripción p300-CBP/metabolismoRESUMEN
Here, we report that the two recently identified E2F subunits, E2F7 and E2F8, are induced in cells treated with DNA-damaging agents where they have an important role in dictating the outcome of the DNA-damage response. The DNA-damage-dependent induction coincides with the binding of E2F7 and E2F8 to the promoters of certain E2F-responsive genes, most notably that of the E2F1 gene, in which E2F7 and E2F8 coexist in a DNA-binding complex. As a consequence, E2F7 and E2F8 repress E2F target genes, such as E2F1, and reducing the level of each subunit results in an increase in E2F1 expression and activity. Importantly, depletion of either E2F7 or E2F8 prevents the cell-cycle effects that occur in response to DNA damage. Thus, E2F7 and E2F8 act upstream of E2F1, and influence the ability of cells to undergo a DNA-damage response. E2F7 and E2F8, therefore, underpin the DNA-damage response.