Identification of an enhancer that increases miR-200b~200a~429 gene expression in breast cancer cells.

The miR-200b~200a~429 gene cluster is a key regulator of EMT and cancer metastasis, however the transcription-based mechanisms controlling its expression during this process are not well understood. We have analyzed the miR-200b~200a~429 locus for epigenetic modifications in breast epithelial and me...

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Autores principales:	Joanne L Attema, Andrew G Bert, Yat-Yuen Lim, Natasha Kolesnikoff, David M Lawrence, Katherine A Pillman, Eric Smith, Paul A Drew, Yeesim Khew-Goodall, Frances Shannon, Gregory J Goodall
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a59b1b8a8d0d4780929167d1d70fe099
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spelling	oai:doaj.org-article:a59b1b8a8d0d4780929167d1d70fe0992021-11-18T08:53:49ZIdentification of an enhancer that increases miR-200b~200a~429 gene expression in breast cancer cells.1932-620310.1371/journal.pone.0075517https://doaj.org/article/a59b1b8a8d0d4780929167d1d70fe0992013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24086551/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203The miR-200b~200a~429 gene cluster is a key regulator of EMT and cancer metastasis, however the transcription-based mechanisms controlling its expression during this process are not well understood. We have analyzed the miR-200b~200a~429 locus for epigenetic modifications in breast epithelial and mesenchymal cell lines using chromatin immunoprecipitation assays and DNA methylation analysis. We discovered a novel enhancer located approximately 5.1kb upstream of the miR-200b~200a~429 transcriptional start site. This region was associated with the active enhancer chromatin signature comprising H3K4me1, H3K27ac, RNA polymerase II and CpG dinucleotide hypomethylation. Luciferase reporter assays revealed the upstream enhancer stimulated the transcription of the miR-200b~200a~429 minimal promoter region approximately 27-fold in breast epithelial cells. Furthermore, we found that a region of the enhancer was transcribed, producing a short, GC-rich, mainly nuclear, non-polyadenylated RNA transcript designated miR-200b eRNA. Over-expression of miR-200b eRNA had little effect on miR-200b~200a~429 promoter activity and its production did not correlate with miR-200b~200a~429 gene expression. While additional investigations of miR-200b eRNA function will be necessary, it is possible that miR-200b eRNA may be involved in the regulation of miR-200b~200a~429 gene expression and silencing. Taken together, these findings reveal the presence of a novel enhancer, which contributes to miR-200b~200a~429 transcriptional regulation in epithelial cells.Joanne L AttemaAndrew G BertYat-Yuen LimNatasha KolesnikoffDavid M LawrenceKatherine A PillmanEric SmithPaul A DrewYeesim Khew-GoodallFrances ShannonGregory J GoodallPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 9, p e75517 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Joanne L Attema Andrew G Bert Yat-Yuen Lim Natasha Kolesnikoff David M Lawrence Katherine A Pillman Eric Smith Paul A Drew Yeesim Khew-Goodall Frances Shannon Gregory J Goodall Identification of an enhancer that increases miR-200b~200a~429 gene expression in breast cancer cells.
description	The miR-200b~200a~429 gene cluster is a key regulator of EMT and cancer metastasis, however the transcription-based mechanisms controlling its expression during this process are not well understood. We have analyzed the miR-200b~200a~429 locus for epigenetic modifications in breast epithelial and mesenchymal cell lines using chromatin immunoprecipitation assays and DNA methylation analysis. We discovered a novel enhancer located approximately 5.1kb upstream of the miR-200b~200a~429 transcriptional start site. This region was associated with the active enhancer chromatin signature comprising H3K4me1, H3K27ac, RNA polymerase II and CpG dinucleotide hypomethylation. Luciferase reporter assays revealed the upstream enhancer stimulated the transcription of the miR-200b~200a~429 minimal promoter region approximately 27-fold in breast epithelial cells. Furthermore, we found that a region of the enhancer was transcribed, producing a short, GC-rich, mainly nuclear, non-polyadenylated RNA transcript designated miR-200b eRNA. Over-expression of miR-200b eRNA had little effect on miR-200b~200a~429 promoter activity and its production did not correlate with miR-200b~200a~429 gene expression. While additional investigations of miR-200b eRNA function will be necessary, it is possible that miR-200b eRNA may be involved in the regulation of miR-200b~200a~429 gene expression and silencing. Taken together, these findings reveal the presence of a novel enhancer, which contributes to miR-200b~200a~429 transcriptional regulation in epithelial cells.
format	article
author	Joanne L Attema Andrew G Bert Yat-Yuen Lim Natasha Kolesnikoff David M Lawrence Katherine A Pillman Eric Smith Paul A Drew Yeesim Khew-Goodall Frances Shannon Gregory J Goodall
author_facet	Joanne L Attema Andrew G Bert Yat-Yuen Lim Natasha Kolesnikoff David M Lawrence Katherine A Pillman Eric Smith Paul A Drew Yeesim Khew-Goodall Frances Shannon Gregory J Goodall
author_sort	Joanne L Attema
title	Identification of an enhancer that increases miR-200b~200a~429 gene expression in breast cancer cells.
title_short	Identification of an enhancer that increases miR-200b~200a~429 gene expression in breast cancer cells.
title_full	Identification of an enhancer that increases miR-200b~200a~429 gene expression in breast cancer cells.
title_fullStr	Identification of an enhancer that increases miR-200b~200a~429 gene expression in breast cancer cells.
title_full_unstemmed	Identification of an enhancer that increases miR-200b~200a~429 gene expression in breast cancer cells.
title_sort	identification of an enhancer that increases mir-200b~200a~429 gene expression in breast cancer cells.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/a59b1b8a8d0d4780929167d1d70fe099
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Identification of an enhancer that increases miR-200b~200a~429 gene expression in breast cancer cells.

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