The metabolic sensor PASK is a histone 3 kinase that also regulates H3K4 methylation by associating with H3K4 MLL2 methyltransferase complex

• Published in: Nucleic acids research Vol. 47; no. 19; pp. 10086 - 10103
• Main Authors: Karakkat, Jimsheena V, Kaimala, Suneesh, Sreedharan, Sreejisha P, Jayaprakash, Princy, Adeghate, Ernest A, Ansari, Suraiya A, Guccione, Ernesto, Mensah-Brown, Eric P K, Starling Emerald, Bright
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 04.11.2019
• Subjects: Animals; Cell Differentiation - genetics; Cell Line; DNA Methylation - genetics; DNA-Binding Proteins - chemistry; DNA-Binding Proteins - genetics; Gene regulation, Chromatin and Epigenetics; HEK293 Cells; Histone Code - genetics; Histones - chemistry; Histones - genetics; Humans; Methyltransferases - genetics; Mice; Multiprotein Complexes - chemistry; Multiprotein Complexes - genetics; Neoplasm Proteins - chemistry; Neoplasm Proteins - genetics; Phosphorylation - genetics; Protamine Kinase - chemistry; Protamine Kinase - genetics; Protein-Serine-Threonine Kinases - chemistry; Protein-Serine-Threonine Kinases - genetics; Satellite Cells, Skeletal Muscle - metabolism; Sequence Analysis, RNA
• ISSN: 0305-1048; 1362-4962
• DOI: 10.1093/nar/gkz786

Abstract The metabolic sensor Per-Arnt-Sim (Pas) domain-containing serine/threonine kinase (PASK) is expressed predominantly in the cytoplasm of different cell types, although a small percentage is also expressed in the nucleus. Herein, we show that the nuclear PASK associates with the mammalian H3K4 MLL2 methyltransferase complex and enhances H3K4 di- and tri-methylation. We also show that PASK is a histone kinase that phosphorylates H3 at T3, T6, S10 and T11. Taken together, these results suggest that PASK regulates two different H3 tail modifications involving H3K4 methylation and H3 phosphorylation. Using muscle satellite cell differentiation and functional analysis after loss or gain of Pask expression using the CRISPR/Cas9 system, we provide evidence that some of the regulatory functions of PASK during development and differentiation may occur through the regulation of these histone modifications.