TY - JOUR
T1 - The metabolic sensor PASK is a histone 3 kinase that also regulates H3K4 methylation by associating with H3K4 MLL2 methyltransferase complex
AU - Karakkat, Jimsheena V.
AU - Kaimala, Suneesh
AU - Sreedharan, Sreejisha P.
AU - Jayaprakash, Princy
AU - Adeghate, Ernest A.
AU - Ansari, Suraiya A.
AU - Guccione, Ernesto
AU - Mensah-Brown, Eric P.K.
AU - Starling Emerald, Bright
N1 - Publisher Copyright:
© The Author(s) 2019..
PY - 2019/11/4
Y1 - 2019/11/4
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85074309476&partnerID=8YFLogxK
U2 - 10.1093/nar/gkz786
DO - 10.1093/nar/gkz786
M3 - Article
C2 - 31529049
AN - SCOPUS:85074309476
SN - 0305-1048
VL - 47
SP - 10086
EP - 10103
JO - Nucleic Acids Research
JF - Nucleic Acids Research
IS - 19
ER -