MEP50/PRMT5 Reduces Gene Expression by Histone Arginine Methylation and this Is Reversed by PKCδ/p38δ Signaling

The Journal of Investigative Dermatology
Kamalika SahaRichard L Eckert

Abstract

Protein kinase C δ (PKCδ) and p38δ are key proteins in a cascade that stimulates keratinocyte differentiation. This cascade activates transcription of involucrin (hINV) and other genes associated with differentiation. Protein arginine methyltransferase 5 (PRMT5) is an arginine methyltransferase that symmetrically dimethylates arginine residues. This protein interacts with a cofactor, methylosome protein 50 (MEP50), and symmetrically dimethylates arginine eight of histone 3 (H3R8me2s) and arginine three of histone 4 (H4R3me2s) to silence gene expression. We use the hINV gene as a tool to understand the relationship between PKCδ/p38δ and PRMT5/MEP50 signaling. MEP50 suppresses hINV mRNA level and promoter activity. This is associated with increased arginine dimethylation of hINV gene-associated H3/H4. We further show that the PKCδ/p38δ keratinocyte differentiation cascade reduces PRMT5 and MEP50 expression, association with the hINV gene promoter, and H3R8me2s and H4R2me2s formation. We propose that PRMT5/MEP50-dependent methylation is an epigenetic mechanism that assists in silencing of hINV expression, and that PKCδ signaling activates gene expression by directly activating transcription and by suppressing PRMT5/MEP50-dependent...Continue Reading

Citations

Nov 10, 2016·Development·Jacqueline L NorrieSteven A Vokes
May 19, 2019·Cellular and Molecular Life Sciences : CMLS·Benjamin M Lorton, David Shechter
Aug 9, 2017·Proceedings of the National Academy of Sciences of the United States of America·Grigory KrapivinskyDavid E Clapham
Dec 31, 2020·Life Science Alliance·Baskar ChakrapaniArunkumar Dhayalan
Jan 15, 2021·Cells·Jean-Paul BryantYeshavanth Kumar Banasavadi-Siddegowda
Apr 16, 2021·Cancer Gene Therapy·Elena BeketovaChang-Deng Hu
Apr 20, 2021·Molecular Carcinogenesis·Geraldine EzekaRichard L Eckert
Jun 22, 2021·PLoS Genetics·Aurélie QuillienLaurence Vandel

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Methods Mentioned

BETA
ChIP
immunoprecipitation assay
immunoprecipitation

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