Growth Factor-induced Activation of MSK2 Leads to Phosphorylation of H3K9me2S10 and Corresponding Changes in Gene Expression

Overview

Journal Sci Adv

Specialties Biology
Science

Date 2024 Mar 13

PMID 38478612

Authors

Karen G Wong

Yu-Chia F Cheng

Vincent H Wu

Anna A Kiseleva

Jun Li

Andrey Poleshko

Cheryl L Smith

Jonathan A Epstein

Affiliations

Soon will be listed here.

Abstract

Extracellular signals are transmitted through kinase cascades to modulate gene expression, but it remains unclear how epigenetic changes regulate this response. Here, we provide evidence that growth factor-stimulated changes in the transcript levels of many responsive genes are accompanied by increases in histone phosphorylation levels, specifically at histone H3 serine-10 when the adjacent lysine-9 is dimethylated (H3K9me2S10). Imaging and proteomic approaches show that epidermal growth factor (EGF) stimulation results in H3K9me2S10 phosphorylation, which occurs in genomic regions enriched for regulatory enhancers of EGF-responsive genes. We also demonstrate that the EGF-induced increase in H3K9me2S10ph is dependent on the nuclear kinase MSK2, and this subset of EGF-induced genes is dependent on MSK2 for transcription. Together, our work indicates that growth factor-induced changes in chromatin state can mediate the activation of downstream genes.

References

Fishilevich S, Nudel R, Rappaport N, Hadar R, Plaschkes I, Iny Stein T . GeneHancer: genome-wide integration of enhancers and target genes in GeneCards. Database (Oxford). 2017; 2017. PMC: 5467550. DOI: 10.1093/database/bax028. View

Van Bortle K, Corces V . Spinning the web of cell fate. Cell. 2013; 152(6):1213-7. PMC: 4018449. DOI: 10.1016/j.cell.2013.02.052. View

Buchwalter A, Kaneshiro J, Hetzer M . Coaching from the sidelines: the nuclear periphery in genome regulation. Nat Rev Genet. 2018; 20(1):39-50. PMC: 6355253. DOI: 10.1038/s41576-018-0063-5. View

Gu Z . Complex heatmap visualization. Imeta. 2024; 1(3):e43. PMC: 10989952. DOI: 10.1002/imt2.43. View

Liberzon A, Birger C, Thorvaldsdottir H, Ghandi M, Mesirov J, Tamayo P . The Molecular Signatures Database (MSigDB) hallmark gene set collection. Cell Syst. 2016; 1(6):417-425. PMC: 4707969. DOI: 10.1016/j.cels.2015.12.004. View

Brand T, Iida M, Li C, Wheeler D . The nuclear epidermal growth factor receptor signaling network and its role in cancer. Discov Med. 2011; 12(66):419-32. PMC: 3305885. View

Haws S, Yu D, Ye C, Wille C, Nguyen L, Krautkramer K . Methyl-Metabolite Depletion Elicits Adaptive Responses to Support Heterochromatin Stability and Epigenetic Persistence. Mol Cell. 2020; 78(2):210-223.e8. PMC: 7191556. DOI: 10.1016/j.molcel.2020.03.004. View

Pearce L, Komander D, Alessi D . The nuts and bolts of AGC protein kinases. Nat Rev Mol Cell Biol. 2009; 11(1):9-22. DOI: 10.1038/nrm2822. View

Sabari B, Tang Z, Huang H, Yong-Gonzalez V, Molina H, Kong H . Intracellular crotonyl-CoA stimulates transcription through p300-catalyzed histone crotonylation. Mol Cell. 2015; 58(2):203-15. PMC: 4501262. DOI: 10.1016/j.molcel.2015.02.029. View

10.

Smith C, Poleshko A, Epstein J . The nuclear periphery is a scaffold for tissue-specific enhancers. Nucleic Acids Res. 2021; 49(11):6181-6195. PMC: 8216274. DOI: 10.1093/nar/gkab392. View

11.

Langmead B, Wilks C, Antonescu V, Charles R . Scaling read aligners to hundreds of threads on general-purpose processors. Bioinformatics. 2018; 35(3):421-432. PMC: 6361242. DOI: 10.1093/bioinformatics/bty648. View

12.

McCarthy D, Chen Y, Smyth G . Differential expression analysis of multifactor RNA-Seq experiments with respect to biological variation. Nucleic Acids Res. 2012; 40(10):4288-97. PMC: 3378882. DOI: 10.1093/nar/gks042. View

13.

Reid M, Dai Z, Locasale J . The impact of cellular metabolism on chromatin dynamics and epigenetics. Nat Cell Biol. 2017; 19(11):1298-1306. PMC: 5886854. DOI: 10.1038/ncb3629. View

14.

Eberlin A, Grauffel C, Oulad-Abdelghani M, Robert F, Torres-Padilla M, Lambrot R . Histone H3 tails containing dimethylated lysine and adjacent phosphorylated serine modifications adopt a specific conformation during mitosis and meiosis. Mol Cell Biol. 2008; 28(5):1739-54. PMC: 2258789. DOI: 10.1128/MCB.01180-07. View

15.

Lin S, Wein S, Gonzales-Cope M, Otte G, Yuan Z, Afjehi-Sadat L . Stable-isotope-labeled histone peptide library for histone post-translational modification and variant quantification by mass spectrometry. Mol Cell Proteomics. 2014; 13(9):2450-66. PMC: 4159661. DOI: 10.1074/mcp.O113.036459. View

16.

Fischle W, Wang Y, Allis C . Binary switches and modification cassettes in histone biology and beyond. Nature. 2003; 425(6957):475-9. DOI: 10.1038/nature02017. View

17.

Regnard C, Straub T, Mitterweger A, Dahlsveen I, Fabian V, Becker P . Global analysis of the relationship between JIL-1 kinase and transcription. PLoS Genet. 2011; 7(3):e1001327. PMC: 3053325. DOI: 10.1371/journal.pgen.1001327. View

18.

Liberzon A, Subramanian A, Pinchback R, Thorvaldsdottir H, Tamayo P, Mesirov J . Molecular signatures database (MSigDB) 3.0. Bioinformatics. 2011; 27(12):1739-40. PMC: 3106198. DOI: 10.1093/bioinformatics/btr260. View

19.

Chen C, Goyal P, Karimi M, Abildgaard M, Kimura H, Lorincz M . H3S10ph broadly marks early-replicating domains in interphase ESCs and shows reciprocal antagonism with H3K9me2. Genome Res. 2017; 28(1):37-51. PMC: 5749181. DOI: 10.1101/gr.224717.117. View

20.

Poleshko A, Smith C, Nguyen S, Sivaramakrishnan P, Wong K, Murray J . H3K9me2 orchestrates inheritance of spatial positioning of peripheral heterochromatin through mitosis. Elife. 2019; 8. PMC: 6795522. DOI: 10.7554/eLife.49278. View