RESUMEN
The bZIP transcription factor ATF6α is a master regulator of endoplasmic reticulum (ER) stress response genes. In this report, we identify the multifunctional RNA polymerase II transcription factor Elongin as a cofactor for ATF6α-dependent transcription activation. Biochemical studies reveal that Elongin functions at least in part by facilitating ATF6α-dependent loading of Mediator at the promoters and enhancers of ER stress response genes. Depletion of Elongin from cells leads to impaired transcription of ER stress response genes and to defects in the recruitment of Mediator and its CDK8 kinase subunit. Taken together, these findings bring to light a role for Elongin as a loading factor for Mediator during the ER stress response.
Asunto(s)
Factor de Transcripción Activador 6/metabolismo , Elonguina/metabolismo , Estrés del Retículo Endoplásmico , Regulación de la Expresión Génica , Complejo Mediador/metabolismo , ARN Polimerasa II/metabolismo , Factor de Transcripción Activador 6/genética , Animales , Elonguina/genética , Retículo Endoplásmico/metabolismo , Retículo Endoplásmico/patología , Células HeLa , Humanos , Complejo Mediador/genética , Regiones Promotoras Genéticas , ARN Polimerasa II/genética , Ratas , Transducción de Señal , Activación TranscripcionalRESUMEN
FACT (facilitates chromatin transcription) is an evolutionarily conserved histone chaperone that was initially identified as an activity capable of promoting RNA polymerase II (Pol II) transcription through nucleosomes in vitro. In this report, we describe a global analysis of FACT function in Pol II transcription in Drosophila. We present evidence that loss of FACT has a dramatic impact on Pol II elongation-coupled processes including histone H3 lysine 4 (H3K4) and H3K36 methylation, consistent with a role for FACT in coordinating histone modification and chromatin architecture during Pol II transcription. Importantly, we identify a role for FACT in the maintenance of promoter-proximal Pol II pausing, a key step in transcription activation in higher eukaryotes. These findings bring to light a broader role for FACT in the regulation of Pol II transcription.