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

doi:10.7554/eLife.17985

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

Biology

Research output: Contribution to journal › Article › peer-review

13 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 language	English
Article number	e17985
Journal	eLife
Volume	5
Issue number	September
DOIs	https://doi.org/10.7554/eLife.17985
State	Published - Sep 23 2016

Bibliographical note

Publisher Copyright:
© Kikani et al.

Funding

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

Funders	Funder number
National Heart, Lung, and Blood Institute (NHLBI)
National Institute of General Medical Sciences	R01GM038663
National Institute of Diabetes and Digestive and Kidney Diseases	5R01DK071962-08

ASJC Scopus subject areas

General Neuroscience
General Immunology and Microbiology
General Biochemistry, Genetics and Molecular Biology

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10.7554/eLife.17985

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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.",

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AU - Wu, Xiaoying

AU - Paul, Litty

AU - Sabic, Hana

AU - Shen, Zuolian

AU - Shakya, Arvind

AU - Keefe, Alexandra

AU - Villanueva, Claudio

AU - Kardon, Gabrielle

AU - Graves, Barbara

AU - Tantin, Dean

AU - Rutter, Jared

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N2 - 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.

AB - 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.

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

Abstract

Bibliographical note

Funding

ASJC Scopus subject areas

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