Dysregulated recruitment of the histone methyltransferase EZH2 to the class II transactivator (CIITA) promoter IV in breast cancer cells.

PloS One
Agnieszka D TruaxSusanna F Greer

Abstract

One mechanism frequently utilized by tumor cells to escape immune system recognition and elimination is suppression of cell surface expression of Major Histocompatibility Class II (MHC II) molecules. Expression of MHC II is regulated primarily at the level of transcription by the Class II Transactivator, CIITA, and decreased CIITA expression is observed in multiple tumor types. We investigate here contributions of epigenetic modifications to transcriptional silencing of CIITA in variants of the human breast cancer cell line MDA MB 435. Significant increases in histone H3 lysine 27 trimethylation upon IFN-γ stimulation correlate with reductions in transcription factor recruitment to the interferon-γ inducible CIITA promoter, CIITApIV, and with significantly increased CIITApIV occupancy by the histone methyltransferase enhancer of zeste homolog 2 (EZH2). Most compelling is evidence that decreased expression of EZH2 in MDA MB 435 variants results in significant increases in CIITA and HLA-DRA mRNA expression, even in the absence of interferon-γ stimulation, as well as increased cell surface expression of MHC II. Together, these data add mechanistic insight to prior observations of increased EZH2 expression and decreased CIITA expre...Continue Reading

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Citations

Feb 19, 2015·International Journal of Molecular Sciences·JoDi Lynn Osborn, Susanna F Greer
Feb 6, 2016·Nature Medicine·Kimberly H Kim, Charles W M Roberts
Aug 19, 2015·Molecular Immunology·Nathaniel H BoydSusanna F Greer
May 7, 2013·Epigenetics : Official Journal of the DNA Methylation Society·Gauri DebSanjay Gupta
Jun 2, 2015·PloS One·Mohamed Abou El HassanRod Bremner
Apr 12, 2015·The Journal of Immunology : Official Journal of the American Association of Immunologists·Mohamed Abou El HassanRod Bremner
Mar 12, 2019·Oncology Letters·Chuntao SunZhihua Zhao
Dec 25, 2019·Signal Transduction and Targeted Therapy·Yuan ChengXiawei Wei
Sep 16, 2020·Nature Reviews. Drug Discovery·Simon J HoggRicky W Johnstone
Jan 16, 2019·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Mrinal M GounderTravis J Hollmann
Dec 17, 2020·Signal Transduction and Targeted Therapy·Yuan ChengXiawei Wei
Sep 26, 2020·Trends in Immunology·Hye-Jung KimKat Cosmopoulos

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Methods Mentioned

BETA
acetylation
MDA
transfection
Immunoprecipitation
ChIP
PCR
acetylate
histone acetylation

Software Mentioned

FlowJo
Flow Jo

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