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Enhancer RNA-driven looping enhances the transcription of the long noncoding RNA DHRS4-AS1, a controller of the DHRS4 gene cluster
The human DHRS4 gene cluster consists of DHRS4 and two immediately downstream homologous genes, DHRS4L2 and DHRS4L1, generated by evolutionarily gene-duplication events. We previously demonstrated that a head-to-head natural antisense transcript (NAT) of DHRS4, denoted DHRS4-AS1, regulates all three...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4750091/ https://www.ncbi.nlm.nih.gov/pubmed/26864944 http://dx.doi.org/10.1038/srep20961 |
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author | Yang, Yingying Su, Zhongjing Song, Xuhong Liang, Bin Zeng, Fanxing Chang, Xiaolan Huang, Dongyang |
author_facet | Yang, Yingying Su, Zhongjing Song, Xuhong Liang, Bin Zeng, Fanxing Chang, Xiaolan Huang, Dongyang |
author_sort | Yang, Yingying |
collection | PubMed |
description | The human DHRS4 gene cluster consists of DHRS4 and two immediately downstream homologous genes, DHRS4L2 and DHRS4L1, generated by evolutionarily gene-duplication events. We previously demonstrated that a head-to-head natural antisense transcript (NAT) of DHRS4, denoted DHRS4-AS1, regulates all three genes of the DHRS4 gene cluster. However, it is puzzling that DHRS4L2 and DHRS4L1 did not evolve their own specific NATs to regulate themselves, as it seems both have retained sequences highly homologous to DHRS4-AS1. In a search of the DHRS4-AS1 region for nearby enhancers, we identified an enhancer located 13.8 kb downstream of the DHRS4-AS1 transcriptional start site. We further showed, by using a chromosome conformation capture (3C) assay, that this enhancer is capable of physically interacting with the DHRS4-AS1 promoter through chromosomal looping. The enhancer produced an eRNA, termed AS1eRNA, that enhanced DHRS4-AS1 transcription by mediating the spatial interactions of the enhancer and DHRS4-AS1 promoter in cooperation with RNA polymerase II and p300/CBP. Moreover, the distributions of activating acetyl-H3 and H3K4me3 modifications were found to be greater at the DHRS4-AS1 promoter than at the homologous duplicated regions. We propose that AS1eRNA-driven DNA looping and activating histone modifications promote the expression of DHRS4-AS1 to economically control the DHRS4 gene cluster. |
format | Online Article Text |
id | pubmed-4750091 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-47500912016-02-18 Enhancer RNA-driven looping enhances the transcription of the long noncoding RNA DHRS4-AS1, a controller of the DHRS4 gene cluster Yang, Yingying Su, Zhongjing Song, Xuhong Liang, Bin Zeng, Fanxing Chang, Xiaolan Huang, Dongyang Sci Rep Article The human DHRS4 gene cluster consists of DHRS4 and two immediately downstream homologous genes, DHRS4L2 and DHRS4L1, generated by evolutionarily gene-duplication events. We previously demonstrated that a head-to-head natural antisense transcript (NAT) of DHRS4, denoted DHRS4-AS1, regulates all three genes of the DHRS4 gene cluster. However, it is puzzling that DHRS4L2 and DHRS4L1 did not evolve their own specific NATs to regulate themselves, as it seems both have retained sequences highly homologous to DHRS4-AS1. In a search of the DHRS4-AS1 region for nearby enhancers, we identified an enhancer located 13.8 kb downstream of the DHRS4-AS1 transcriptional start site. We further showed, by using a chromosome conformation capture (3C) assay, that this enhancer is capable of physically interacting with the DHRS4-AS1 promoter through chromosomal looping. The enhancer produced an eRNA, termed AS1eRNA, that enhanced DHRS4-AS1 transcription by mediating the spatial interactions of the enhancer and DHRS4-AS1 promoter in cooperation with RNA polymerase II and p300/CBP. Moreover, the distributions of activating acetyl-H3 and H3K4me3 modifications were found to be greater at the DHRS4-AS1 promoter than at the homologous duplicated regions. We propose that AS1eRNA-driven DNA looping and activating histone modifications promote the expression of DHRS4-AS1 to economically control the DHRS4 gene cluster. Nature Publishing Group 2016-02-11 /pmc/articles/PMC4750091/ /pubmed/26864944 http://dx.doi.org/10.1038/srep20961 Text en Copyright © 2016, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Yang, Yingying Su, Zhongjing Song, Xuhong Liang, Bin Zeng, Fanxing Chang, Xiaolan Huang, Dongyang Enhancer RNA-driven looping enhances the transcription of the long noncoding RNA DHRS4-AS1, a controller of the DHRS4 gene cluster |
title | Enhancer RNA-driven looping enhances the transcription of the long noncoding RNA DHRS4-AS1, a controller of the DHRS4 gene cluster |
title_full | Enhancer RNA-driven looping enhances the transcription of the long noncoding RNA DHRS4-AS1, a controller of the DHRS4 gene cluster |
title_fullStr | Enhancer RNA-driven looping enhances the transcription of the long noncoding RNA DHRS4-AS1, a controller of the DHRS4 gene cluster |
title_full_unstemmed | Enhancer RNA-driven looping enhances the transcription of the long noncoding RNA DHRS4-AS1, a controller of the DHRS4 gene cluster |
title_short | Enhancer RNA-driven looping enhances the transcription of the long noncoding RNA DHRS4-AS1, a controller of the DHRS4 gene cluster |
title_sort | enhancer rna-driven looping enhances the transcription of the long noncoding rna dhrs4-as1, a controller of the dhrs4 gene cluster |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4750091/ https://www.ncbi.nlm.nih.gov/pubmed/26864944 http://dx.doi.org/10.1038/srep20961 |
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