Cargando…

The CpG Island Encompassing the Promoter and First Exon of Human DNMT3L Gene Is a PcG/TrX Response Element (PRE)

DNMT3L, a member of DNA methyltransferases family, is present only in mammals. As it provides specificity to the action of de novo methyltransferases, DNMT3A and DNMT3B and interacts with histone H3, DNMT3L has been invoked as the molecule that can read the histone code and translate it into DNA met...

Descripción completa

Detalles Bibliográficos
Autores principales: Basu, Amitava, Dasari, Vasanthi, Mishra, Rakesh K., Khosla, Sanjeev
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3990577/
https://www.ncbi.nlm.nih.gov/pubmed/24743422
http://dx.doi.org/10.1371/journal.pone.0093561
_version_ 1782312305483055104
author Basu, Amitava
Dasari, Vasanthi
Mishra, Rakesh K.
Khosla, Sanjeev
author_facet Basu, Amitava
Dasari, Vasanthi
Mishra, Rakesh K.
Khosla, Sanjeev
author_sort Basu, Amitava
collection PubMed
description DNMT3L, a member of DNA methyltransferases family, is present only in mammals. As it provides specificity to the action of de novo methyltransferases, DNMT3A and DNMT3B and interacts with histone H3, DNMT3L has been invoked as the molecule that can read the histone code and translate it into DNA methylation. It plays an important role in the initiation of genomic imprints during gametogenesis and in nuclear reprogramming. With important functions attributed to it, it is imperative that the DNMT3L expression is tightly controlled. Previously, we had identified a CpG island within the human DNMT3L promoter and first exon that showed loss of DNA methylation in cancer samples. Here we show that this Differentially Methylated CpG island within DNMT3L (DNMT3L DMC) acts to repress transcription, is a Polycomb/Trithorax Response Element (PRE) and interacts with both PRC1 and PRC2 Polycomb repressive complexes. In addition, it adopts inactive chromatin conformation and is associated with other inactive chromatin-specific proteins like SUV39H1 and HP1. The presence of DNMT3L DMC also influences the adjacent promoter to adopt repressive histone post-translational modifications. Due to its association with multiple layers of repressive epigenetic modifications, we believe that PRE within the DNMT3L DMC is responsible for the tight regulation of DNMT3L expression and the aberrant epigenetic modifications of this region leading to DNMT3L overexpression could be the reason of nuclear programming during carcinogenesis.
format Online
Article
Text
id pubmed-3990577
institution National Center for Biotechnology Information
language English
publishDate 2014
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-39905772014-04-21 The CpG Island Encompassing the Promoter and First Exon of Human DNMT3L Gene Is a PcG/TrX Response Element (PRE) Basu, Amitava Dasari, Vasanthi Mishra, Rakesh K. Khosla, Sanjeev PLoS One Research Article DNMT3L, a member of DNA methyltransferases family, is present only in mammals. As it provides specificity to the action of de novo methyltransferases, DNMT3A and DNMT3B and interacts with histone H3, DNMT3L has been invoked as the molecule that can read the histone code and translate it into DNA methylation. It plays an important role in the initiation of genomic imprints during gametogenesis and in nuclear reprogramming. With important functions attributed to it, it is imperative that the DNMT3L expression is tightly controlled. Previously, we had identified a CpG island within the human DNMT3L promoter and first exon that showed loss of DNA methylation in cancer samples. Here we show that this Differentially Methylated CpG island within DNMT3L (DNMT3L DMC) acts to repress transcription, is a Polycomb/Trithorax Response Element (PRE) and interacts with both PRC1 and PRC2 Polycomb repressive complexes. In addition, it adopts inactive chromatin conformation and is associated with other inactive chromatin-specific proteins like SUV39H1 and HP1. The presence of DNMT3L DMC also influences the adjacent promoter to adopt repressive histone post-translational modifications. Due to its association with multiple layers of repressive epigenetic modifications, we believe that PRE within the DNMT3L DMC is responsible for the tight regulation of DNMT3L expression and the aberrant epigenetic modifications of this region leading to DNMT3L overexpression could be the reason of nuclear programming during carcinogenesis. Public Library of Science 2014-04-17 /pmc/articles/PMC3990577/ /pubmed/24743422 http://dx.doi.org/10.1371/journal.pone.0093561 Text en © 2014 Basu et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Basu, Amitava
Dasari, Vasanthi
Mishra, Rakesh K.
Khosla, Sanjeev
The CpG Island Encompassing the Promoter and First Exon of Human DNMT3L Gene Is a PcG/TrX Response Element (PRE)
title The CpG Island Encompassing the Promoter and First Exon of Human DNMT3L Gene Is a PcG/TrX Response Element (PRE)
title_full The CpG Island Encompassing the Promoter and First Exon of Human DNMT3L Gene Is a PcG/TrX Response Element (PRE)
title_fullStr The CpG Island Encompassing the Promoter and First Exon of Human DNMT3L Gene Is a PcG/TrX Response Element (PRE)
title_full_unstemmed The CpG Island Encompassing the Promoter and First Exon of Human DNMT3L Gene Is a PcG/TrX Response Element (PRE)
title_short The CpG Island Encompassing the Promoter and First Exon of Human DNMT3L Gene Is a PcG/TrX Response Element (PRE)
title_sort cpg island encompassing the promoter and first exon of human dnmt3l gene is a pcg/trx response element (pre)
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3990577/
https://www.ncbi.nlm.nih.gov/pubmed/24743422
http://dx.doi.org/10.1371/journal.pone.0093561
work_keys_str_mv AT basuamitava thecpgislandencompassingthepromoterandfirstexonofhumandnmt3lgeneisapcgtrxresponseelementpre
AT dasarivasanthi thecpgislandencompassingthepromoterandfirstexonofhumandnmt3lgeneisapcgtrxresponseelementpre
AT mishrarakeshk thecpgislandencompassingthepromoterandfirstexonofhumandnmt3lgeneisapcgtrxresponseelementpre
AT khoslasanjeev thecpgislandencompassingthepromoterandfirstexonofhumandnmt3lgeneisapcgtrxresponseelementpre
AT basuamitava cpgislandencompassingthepromoterandfirstexonofhumandnmt3lgeneisapcgtrxresponseelementpre
AT dasarivasanthi cpgislandencompassingthepromoterandfirstexonofhumandnmt3lgeneisapcgtrxresponseelementpre
AT mishrarakeshk cpgislandencompassingthepromoterandfirstexonofhumandnmt3lgeneisapcgtrxresponseelementpre
AT khoslasanjeev cpgislandencompassingthepromoterandfirstexonofhumandnmt3lgeneisapcgtrxresponseelementpre