Polycomb/Trithorax Antagonism: Cellular Memory in Stem Cell Fate and Function

Overview

Journal Cell Stem Cell

Publisher Cell Press

Specialty Cell Biology

Date 2019 Apr 6

PMID 30951661

Citations 32

Authors

Marjorie Brand

Kiran Nakka

Jiayu Zhu

F Jeffrey Dilworth

Affiliations

Soon will be listed here.

Abstract

Stem cells are continuously challenged with the decision to either self-renew or adopt a new fate. Self-renewal is regulated by a system of cellular memory, which must be bypassed for differentiation. Previous studies have identified Polycomb group (PcG) and Trithorax group (TrxG) proteins as key modulators of cellular memory. In this Perspective, we draw from embryonic and adult stem cell studies to discuss the complex roles played by PcG and TrxG in maintaining cell identity while allowing for microenvironment-mediated alterations in cell fate. Finally, we discuss the potential for targeting these proteins as a therapeutic approach in cancer.

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References

Dorighi K, Swigut T, Henriques T, Bhanu N, Scruggs B, Nady N . Mll3 and Mll4 Facilitate Enhancer RNA Synthesis and Transcription from Promoters Independently of H3K4 Monomethylation. Mol Cell. 2017; 66(4):568-576.e4. PMC: 5662137. DOI: 10.1016/j.molcel.2017.04.018. View

Fernandez-Alonso R, Bustos F, Williams C, Findlay G . Protein Kinases in Pluripotency-Beyond the Usual Suspects. J Mol Biol. 2017; 429(10):1504-1520. DOI: 10.1016/j.jmb.2017.04.013. View

Beguelin W, Popovic R, Teater M, Jiang Y, Bunting K, Rosen M . EZH2 is required for germinal center formation and somatic EZH2 mutations promote lymphoid transformation. Cancer Cell. 2013; 23(5):677-92. PMC: 3681809. DOI: 10.1016/j.ccr.2013.04.011. View

Brand M, Dilworth F . Splicing of Ezh1 gets muscle out of stressful situations. Nat Struct Mol Biol. 2017; 24(5):435-437. DOI: 10.1038/nsmb.3406. View

Faralli H, Wang C, Nakka K, Benyoucef A, Sebastian S, Zhuang L . UTX demethylase activity is required for satellite cell-mediated muscle regeneration. J Clin Invest. 2016; 126(4):1555-65. PMC: 4811158. DOI: 10.1172/JCI83239. View

Robson L, Di Foggia V, Radunovic A, Bird K, Zhang X, Marino S . Bmi1 is expressed in postnatal myogenic satellite cells, controls their maintenance and plays an essential role in repeated muscle regeneration. PLoS One. 2011; 6(11):e27116. PMC: 3212532. DOI: 10.1371/journal.pone.0027116. View

Roch A, Trachsel V, Lutolf M . Brief Report: Single-Cell Analysis Reveals Cell Division-Independent Emergence of Megakaryocytes From Phenotypic Hematopoietic Stem Cells. Stem Cells. 2015; 33(10):3152-7. DOI: 10.1002/stem.2106. View

Berg T, Thoene S, Yap D, Wee T, Schoeler N, Rosten P . A transgenic mouse model demonstrating the oncogenic role of mutations in the polycomb-group gene EZH2 in lymphomagenesis. Blood. 2014; 123(25):3914-24. DOI: 10.1182/blood-2012-12-473439. View

Wang C, Lee J, Cho Y, Xiao Y, Jin Q, Liu C . UTX regulates mesoderm differentiation of embryonic stem cells independent of H3K27 demethylase activity. Proc Natl Acad Sci U S A. 2012; 109(38):15324-9. PMC: 3458330. DOI: 10.1073/pnas.1204166109. View

10.

Xie G, Liu X, Zhang Y, Li W, Liu S, Chen Z . UTX promotes hormonally responsive breast carcinogenesis through feed-forward transcription regulation with estrogen receptor. Oncogene. 2017; 36(39):5497-5511. DOI: 10.1038/onc.2017.157. View

11.

Yu M, Mazor T, Huang H, Huang H, Kathrein K, Woo A . Direct recruitment of polycomb repressive complex 1 to chromatin by core binding transcription factors. Mol Cell. 2012; 45(3):330-43. PMC: 3278717. DOI: 10.1016/j.molcel.2011.11.032. View

12.

Grzenda A, Lomberk G, Svingen P, Mathison A, Calvo E, Iovanna J . Functional characterization of EZH2β reveals the increased complexity of EZH2 isoforms involved in the regulation of mammalian gene expression. Epigenetics Chromatin. 2013; 6(1):3. PMC: 3606351. DOI: 10.1186/1756-8935-6-3. View

13.

Chen K, Xiao H, Zeng J, Yu G, Zhou H, Huang C . Alternative Splicing of EZH2 pre-mRNA by SF3B3 Contributes to the Tumorigenic Potential of Renal Cancer. Clin Cancer Res. 2016; 23(13):3428-3441. PMC: 5440213. DOI: 10.1158/1078-0432.CCR-16-2020. View

14.

Hu D, Gao X, Morgan M, Herz H, Smith E, Shilatifard A . The MLL3/MLL4 branches of the COMPASS family function as major histone H3K4 monomethylases at enhancers. Mol Cell Biol. 2013; 33(23):4745-54. PMC: 3838007. DOI: 10.1128/MCB.01181-13. View

15.

Andricovich J, Perkail S, Kai Y, Casasanta N, Peng W, Tzatsos A . Loss of KDM6A Activates Super-Enhancers to Induce Gender-Specific Squamous-like Pancreatic Cancer and Confers Sensitivity to BET Inhibitors. Cancer Cell. 2018; 33(3):512-526.e8. PMC: 5854186. DOI: 10.1016/j.ccell.2018.02.003. View

16.

Xie J, Fan C, Zhang J, Zhang S . Expression specificity and compensation effect of Ash2l-1/Ash2l-2 in mouse embryonic stem cells. Yi Chuan. 2018; 40(3):237-249. DOI: 10.16288/j.yczz.17-284. View

17.

Beltran M, Yates C, Skalska L, Dawson M, Reis F, Viiri K . The interaction of PRC2 with RNA or chromatin is mutually antagonistic. Genome Res. 2016; 26(7):896-907. PMC: 4937559. DOI: 10.1101/gr.197632.115. View

18.

Kamps J, Huang J, Poater J, Xu C, Pieters B, Dong A . Chemical basis for the recognition of trimethyllysine by epigenetic reader proteins. Nat Commun. 2015; 6:8911. PMC: 4673829. DOI: 10.1038/ncomms9911. View

19.

Kim E, Ilagan J, Liang Y, Daubner G, Lee S, Ramakrishnan A . SRSF2 Mutations Contribute to Myelodysplasia by Mutant-Specific Effects on Exon Recognition. Cancer Cell. 2015; 27(5):617-30. PMC: 4429920. DOI: 10.1016/j.ccell.2015.04.006. View

20.

Ikawa T, Masuda K, Endo T, Endo M, Isono K, Koseki Y . Conversion of T cells to B cells by inactivation of polycomb-mediated epigenetic suppression of the B-lineage program. Genes Dev. 2016; 30(22):2475-2485. PMC: 5159663. DOI: 10.1101/gad.290593.116. View