Dual histone reader ZMYND8 inhibits cancer cell invasion by positively regulating epithelial genes
IR@IICB: CSIR-Indian Institute of Chemical Biology, Kolkata
View Archive Info| Field | Value | |
| Title |
Dual histone reader ZMYND8 inhibits cancer cell
invasion by positively regulating epithelial genes
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| Creator |
Basu, Moitri
Sengupta, Isha Kha, Md Wasim Srivastava, Dushyant Kumar Chakrabart, Partha Roy, Siddhartha Das, Chandrima |
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| Subject |
Cell Biology & Physiology
Structural Biology & Bioinformatics |
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| Description |
Enhanced migratory potential and invasiveness of cancer cells contribute crucially to cancer progression. These phenotypes are achieved by precise alteration of invasionassociated genes through local epigenetic modifications which are recognized by a class
of proteins termed a chromatin reader. ZMYND8 [zinc finger MYND (myeloid, Nervy and DEAF-1)-type containing 8], a key component of the transcription regulatory network, has
recently been shown to be a novel reader of H3.1K36Me2/H4K16Ac marks. Through differential
gene expression analysis upon silencing this chromatin reader, we identified a subset of genes involved in cell proliferation and invasion/migration regulated by
ZMYND8. Detailed analysis uncovered its antiproliferative activity through BrdU incorporation, alteration in the expression of proliferation markers, and cell cycle regulating genes and cell viability assays. In addition, performing wound healing and invasion/migration
assays, its anti-invasive nature is evident. Interestingly, epithelial–mesenchymal transition (EMT), a key mechanism of cellular invasion, is regulated by ZMYND8 where we identified its selective enrichment on promoters of CLDN1/CDH1 genes, rich in H3K36Me2/ H4K16Ac marks, leading to their up-regulation. Thus, the presence of ZMYND8 could be implicated in maintaining the epithelial phenotype of cells. Furthermore, syngeneic mice, injected with ZMYND8-overexpressed invasive breast cancer cells, showed reduction in tumor volume and weight. In concert with this, we observed a significant down-regulation of ZMYND8 in invasive ductal and lobular breast cancer tissues compared with normal tissue. Taken together, our study elucidates a novel function of ZMYND8 in regulating EMT and invasion of cancer cells, possibly through its chromatin reader function.
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| Publisher |
Portland Press
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| Date |
2017-05-19
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| Type |
Article
PeerReviewed |
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| Format |
application/pdf
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| Identifier |
http://www.eprints.iicb.res.in/2677/1/Biochemical_Journal_(2017)_474.pdf
Basu, Moitri and Sengupta, Isha and Kha, Md Wasim and Srivastava, Dushyant Kumar and Chakrabart, Partha and Roy, Siddhartha and Das, Chandrima (2017) Dual histone reader ZMYND8 inhibits cancer cell invasion by positively regulating epithelial genes. Biochemical Journal, 414 (11). pp. 1919-1934. ISSN 0264-6021 |
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| Relation |
http://dx.doi.org/10.1042/BCJ20170223
http://www.eprints.iicb.res.in/2677/ |
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