Pask integrates hormonal signaling with histone modification via Wdr5 phosphorylation to drive myogenesis

eLife

Jared Rutter¹  Hana Sabic¹  Chintan K Kikani²  Zuolian Shen²  Gabrielle Kardon²  Xiaoying Wu²  Barbara Graves³  Claudio Villanueva³  Litty Paul⁴  Dean Tantin⁴  Arvind Shakya⁵  Alexandra Keefe⁵ 

[1] Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, United States;Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, United States;Department of Human Genetics, University of Utah School of Medicine, Salt Lake City, United States;Department of Oncological Sciences, University of Utah School of Medicine, Salt Lake City, United States;Department of Pathology, University of Utah School of Medicine, Salt Lake City, United States;

关键词: PASK;    WDR5;    muscle differentiation;    MyoD;    myogenin;    stem cells;   

DOI  :  10.7554/eLife.17985

来源: DOAJ

【 摘 要 】

PAS domain containing protein kinase (Pask) is an evolutionarily conserved protein kinase implicated in energy homeostasis and metabolic regulation across eukaryotic species. We now describe an unexpected role of Pask in promoting the differentiation of myogenic progenitor cells, embryonic stem cells and adipogenic progenitor cells. This function of Pask is dependent upon its ability to phosphorylate Wdr5, a member of several protein complexes including those that catalyze histone H3 Lysine 4 trimethylation (H3K4me3) during transcriptional activation. Our findings suggest that, during myoblast differentiation, Pask stimulates the conversion of repressive H3K4me1 to activating H3K4me3 marks on the promoter of the differentiation gene myogenin (Myog) via Wdr5 phosphorylation. This enhances accessibility of the MyoD transcription factor and enables transcriptional activation of the Myog promoter to initiate muscle differentiation. Thus, as an upstream kinase of Wdr5, Pask integrates signaling cues with the transcriptional network to regulate the differentiation of progenitor cells.

【 授权许可】

Unknown