A Role for Mediator in Pomc Transcriptional Activation By RNA Polymerase II

Presentation Number: MON-0396
Date of Presentation: June 23rd, 2014

Shinobu Takayasu*1, Jacques Drouin2 and Aurelio Balsalobre2
1Hirosaki Univ Schl of Med, Hirosaki-Shi, Japan, 2Institut de Recherches Cliniques de Montreal, Montreal, QC, Canada

Abstract

The Mediator was purified as a protein complex that facilitates transcription of signal-dependent genes. Mediator is recruited through transcription factor interactions at enhancers and it acts as bridge with core promoters and pre-initiation complexes; loops between enhancers and promoters. It has not clarified which genes use Mediator for transcription, and what is the specific role of Mediator for control of transcription. The signal-dependent recruitment of Mediator Regulatory kinase Cdk8 was observed at hormone-activated promoters where Cdk8 occupancy was correlated with levels of RNA polymerase II phosphorylated at Serine 5 of the C-terminal domain and transcription in highly-differentiated mouse hormone-responsive cells. In contrast, promoter recruitment of Cdk7, the purported Ser5 kinase, was not correlated with transcription. Pituitary POMC gene transcription is regulated by a variety of signals, including activation by the hypothalamic CRH and repression by glucocorticoids that regulate transcription through the GR. POMC gene further indicated that hormonal regulation, both activation and repression, is not reflected in the strength of looping interactions between enhancer and promoter as revealed by chromosome conformation capture but that recruitment of Mediator at enhancers and of Cdk8 at promoter was correlated with activated transcription. In summary, the present work supports a model where the Mediator complex serves a primary role in controlling transcription through activation and delivery of Mediator rather than the strength of interactions between enhancer and promoter.

 

Nothing to Disclose: ST, JD, AB