Abstract
The Mediator complex has been thought as a key regulatory complex of RNA polymerase II (Pol II) and it has been known as bivalent, positive and negative, transcriptional regulator. Mediator complexes were reported to form at least two subtypes, large‐Mediator and small‐Mediator, depending on those subunit compositions. In previous studies, large‐Mediator has been thought to act negatively and small‐Mediator to act positively in transcription. Compared to its roles in transcriptional activation, little has been known in its roles in transcriptional repression. Here I show novel mechanisms of the Mediator complex in transcriptional repression in C/EBPβ target genes. To study a repressive mechanism by large‐Mediator, I purified CDK8 which is the large‐Mediator specific subunit forming complex and discovered PRMT5 as an interaction factor. PRMT5 is known to catalyze repressive histone modification (e.g., H4R3me2s) and recruits DNMT3A to target regions. Therefore, Large‐Mediator specific subunit CDK8 recruits PRMT5 and DNMT3A to certain C/EBPβ target gene promoter regions and represses those genes transcription via epigenetic machinery. This finding highlights a link of the Mediator complex to epigenetic regulation machinery and shows that the Mediator complex acts not only as Pol II recruiter but also as epigenetic regulator in transcription.This study supported by Grant‐in‐Aid for JSPS Fellows.
Published Version
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