Regulation of IL-20 expression by estradiol through KMT2B-mediated epigenetic modification

Chia Hsin Su, I. Hsuan Lin, Tsai Yu Tzeng, Wen Ting Hsieh, Ming Ta Hsu

Research output: Contribution to journalArticle

Abstract

Cytokines are low molecular weight regulatory proteins, or glycoproteins, with both tumorpromoting and inhibitory effects on breast cancer growth. Different cytokines play important roles in breast cancer initiation and progression. Here, we show that of the 39 interleukin (IL) genes, IL-20 is the only gene over-expressed in MCF-7 cells treated with estradiol (E2) and that induction of IL-20 expression by estrogen was epigenetically regulated. Methylation of histone H3K4 in the IL-20 promoter was shown to occur via the specific recruitment of KMT2B by estrogen receptor alpha (ERα), but not by other members of the mixed-lineage leukemia (MLL) family of histone methyltransferases. Depletion of KMT2B, or IL-20, disrupts estrogen signaling, attenuates cell proliferation, reduces colony formation, and results in cell cycle arrest. Furthermore, we demonstrated that KMT2B-mediated epigenetic modification also affected the expression of several ERα target genes. IL-20 and KMT2B expression were also associated with ERα-positive breast cancer tissues. We have revealed an important role for KMT2B in the epigenetic transcriptional regulation of cytokine IL-20, and other ERα-responsive genes, in breast cancer cells. Inhibition of IL-20 and KMT2B may have therapeutic benefits in ERα-positive breast cancer.

Original languageEnglish
Article numbere0166090
JournalPLoS One
Volume11
Issue number11
DOIs
Publication statusPublished - Nov 1 2016

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interleukins
Epigenomics
epigenetics
estradiol
Estradiol
Estrogen Receptor alpha
breast neoplasms
Breast Neoplasms
Genes
cytokines
Cytokines
histones
Estrogens
estrogens
Cells
genes
Methylation
Interleukins
MCF-7 Cells
Cell proliferation

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Regulation of IL-20 expression by estradiol through KMT2B-mediated epigenetic modification. / Su, Chia Hsin; Lin, I. Hsuan; Tzeng, Tsai Yu; Hsieh, Wen Ting; Hsu, Ming Ta.

In: PLoS One, Vol. 11, No. 11, e0166090, 01.11.2016.

Research output: Contribution to journalArticle

Su, Chia Hsin ; Lin, I. Hsuan ; Tzeng, Tsai Yu ; Hsieh, Wen Ting ; Hsu, Ming Ta. / Regulation of IL-20 expression by estradiol through KMT2B-mediated epigenetic modification. In: PLoS One. 2016 ; Vol. 11, No. 11.
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