title: Pask integrates hormonal signaling with histone modification via Wdr5 phosphorylation to drive myogenesis.
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 theMyogpromoter 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.
authors.affiliation: Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, United States.
authors.forename: Chintan K
authors.identifier: 0000-0003-1140-0192
authors.initials: CK
authors.lastname: Kikani
authors.affiliation: Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, United States.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Oncological Sciences, University of Utah School of Medicine, Salt Lake City, United States.|Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, United States.
authors.forename: Litty
authors.initials: L
authors.lastname: Paul
authors.affiliation: Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, United States.
authors.forename: Hana
authors.initials: H
authors.lastname: Sabic
authors.affiliation: Department of Pathology, University of Utah School of Medicine, Salt Lake City, United States.
authors.forename: Zuolian
authors.initials: Z
authors.lastname: Shen
authors.affiliation: Department of Pathology, University of Utah School of Medicine, Salt Lake City, United States.
authors.forename: Arvind
authors.initials: A
authors.lastname: Shakya
authors.affiliation: Department of Human Genetics, University of Utah School of Medicine, Salt Lake City, United States.
authors.forename: Alexandra
authors.identifier: 0000-0001-9947-3403
authors.initials: A
authors.lastname: Keefe
authors.affiliation: Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, United States.
authors.forename: Claudio
authors.initials: C
authors.lastname: Villanueva
authors.affiliation: Department of Human Genetics, University of Utah School of Medicine, Salt Lake City, United States.
authors.forename: Gabrielle
authors.initials: G
authors.lastname: Kardon
authors.affiliation: Department of Oncological Sciences, University of Utah School of Medicine, Salt Lake City, United States.|Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, United States.|Howard Hughes Medical Institute, University of Utah School of Medicine, Salt Lake City, United States.
authors.forename: Barbara
authors.initials: B
authors.lastname: Graves
authors.affiliation: Department of Pathology, University of Utah School of Medicine, Salt Lake City, United States.
authors.forename: Dean
authors.identifier: 0000-0003-1354-8385
authors.initials: D
authors.lastname: Tantin
authors.affiliation: Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, United States.|Howard Hughes Medical Institute, University of Utah School of Medicine, Salt Lake City, United States.
authors.forename: Jared
authors.identifier: 0000-0002-2710-9765
authors.initials: J
authors.lastname: Rutter
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D042421:Histone Code; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D000066450:Mouse Embryonic Stem Cells / Q000378:metabolism; D032342:Muscle Cells / Q000502:physiology; D024510:Muscle Development / Q000502:physiology*; D018482:Muscle, Skeletal; D009132:Muscles / Q000293:injuries / Q000378:metabolism*; D017570:MyoD Protein / Q000378:metabolism; D032446:Myoblasts / Q000473:pathology; D018008:Myogenin / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013234:Stem Cells; D015533:Transcriptional Activation
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C503799:MYOG protein, human; D017570:MyoD Protein; D018008:Myogenin; C502547:WDR5 protein, human; D011495:Histone-Lysine N-Methyltransferase; C116037:PAS domain kinases; D017346:Protein Serine-Threonine Kinases
keywords: MyoD; PASK; WDR5; biochemistry; developmental biology; human; mouse; muscle differentiation; myogenin; stem cells