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

Chintan K. Kikani, Xiaoying Wu, Litty Paul, Hana Sabic, Zuolian Shen, Arvind Shakya, Alexandra Keefe, Claudio Villanueva, Gabrielle Kardon, Barbara Graves, Dean Tantin, Jared Rutter

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

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.

Original languageEnglish
Article numbere17985
JournaleLife
Volume5
Issue numberSeptember
DOIs
StatePublished - Sep 23 2016

Bibliographical note

Funding Information:
National Institute of Diabetes and Digestive and Kidney Diseases 5R01DK071962-08, National Heart, Lung, and Blood Institute Post Doctoral Training Fellowship.

Publisher Copyright:
© Kikani et al.

ASJC Scopus subject areas

  • Neuroscience (all)
  • Immunology and Microbiology (all)
  • Biochemistry, Genetics and Molecular Biology (all)

Fingerprint

Dive into the research topics of 'Pask integrates hormonal signaling with histone modification via Wdr5 phosphorylation to drive myogenesis'. Together they form a unique fingerprint.

Cite this