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RNA transcribed from a distal enhancer is required for activating the chromatin at the promoter of the gonadotropin α-subunit gene.

Since the discovery that many transcriptional enhancers are transcribed into long noncoding RNAs termed "enhancer RNAs" (eRNAs), their putative role in enhancer function has been debated. Very recent evidence has indicted that some eRNAs play a role in initiating or activating transcription, possibl... Full description

Journal Title: Proceedings of the National Academy of Sciences of the United States of America April 7, 2015, Vol.112(14), pp.4369-4374
Main Author: Pnueli, Lilach
Other Authors: Rudnizky, Sergei , Yosefzon, Yahav , Melamed, Philippa
Format: Electronic Article Electronic Article
Language: English
Subjects:
RNA
ID: E-ISSN: 1091-6490 ; DOI: 10.1073/pnas.1414841112
Link: http://search.proquest.com/docview/1672093126/?pq-origsite=primo
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title: RNA transcribed from a distal enhancer is required for activating the chromatin at the promoter of the gonadotropin α-subunit gene.
format: Article
creator:
  • Pnueli, Lilach
  • Rudnizky, Sergei
  • Yosefzon, Yahav
  • Melamed, Philippa
subjects:
  • Animals–Metabolism
  • Cell Line–Genetics
  • Chromatin–Metabolism
  • Chromatin Immunoprecipitation–Metabolism
  • Cpg Islands–Metabolism
  • DNA Methylation–Metabolism
  • Enhancer Elements, Genetic–Metabolism
  • Gene Expression Regulation–Metabolism
  • Glycoprotein Hormones, Alpha Subunit–Metabolism
  • Histones–Metabolism
  • Mice–Metabolism
  • Pituitary Gland–Metabolism
  • Promoter Regions, Genetic–Metabolism
  • RNA–Metabolism
  • RNA, Messenger–Metabolism
  • Chromatin
  • Glycoprotein Hormones, Alpha Subunit
  • Histones
  • RNA, Messenger
  • RNA
  • Chromatin
  • Enhancer
  • Gonadotropin
  • Ncrna
  • Pituitary
ispartof: Proceedings of the National Academy of Sciences of the United States of America, April 7, 2015, Vol.112(14), pp.4369-4374
description: Since the discovery that many transcriptional enhancers are transcribed into long noncoding RNAs termed "enhancer RNAs" (eRNAs), their putative role in enhancer function has been debated. Very recent evidence has indicted that some eRNAs play a role in initiating or activating transcription, possibly by helping recruit and/or stabilize binding of the general transcription machinery to the proximal promoter of their target genes. The distal enhancer of the gonadotropin hormone [alpha]-subunit gene, chorionic gonadotropin alpha (Cga), is responsible for Cga cell-specific expression in gonadotropes and thyrotropes, and we show here that it encodes two bidirectional nonpolyadenylated RNAs whose levels are increased somewhat by exposure to gonadotropin-releasing hormone but are not necessarily linked to Cga transcriptional activity. Knockdown of the more distal eRNA led to a drop in Cga mRNA levels, initially without effect on the forward eRNA levels. With time, however, the repression on the Cga increased, and the forward eRNA levels were suppressed also. We demonstrate that the interaction of the enhancer with the promoter is lost after eRNA knockdown. Dramatic changes also were seen in the chromatin, with an increase in total histone H3 occupancy throughout this region and a virtual loss of histone H3 Lys 4 trimethylation at the promoter following the eRNA knockdown. Moreover, histone H3 Lys 27 (H3K27) acetylation, which was found at both enhancer and promoter in wild-type cells, appeared to have been replaced by H3K27 trimethylation at the enhancer. Thus, the Cga eRNA mediates the physical interaction between these genomic regions and determines the chromatin structure of the proximal promoter to allow gene expression. enhancer | chromatin | ncRNAf | gonadotropin | pituitary
language: eng
source:
identifier: E-ISSN: 1091-6490 ; DOI: 10.1073/pnas.1414841112
fulltext: fulltext
issn:
  • 10916490
  • 1091-6490
url: Link


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titleRNA transcribed from a distal enhancer is required for activating the chromatin at the promoter of the gonadotropin α-subunit gene.
creatorPnueli, Lilach ; Rudnizky, Sergei ; Yosefzon, Yahav ; Melamed, Philippa
contributorPnueli, Lilach (correspondence author) ; Pnueli, Lilach (record owner)
ispartofProceedings of the National Academy of Sciences of the United States of America, April 7, 2015, Vol.112(14), pp.4369-4374
identifierE-ISSN: 1091-6490 ; DOI: 10.1073/pnas.1414841112
subjectAnimals–Metabolism ; Cell Line–Genetics ; Chromatin–Metabolism ; Chromatin Immunoprecipitation–Metabolism ; Cpg Islands–Metabolism ; DNA Methylation–Metabolism ; Enhancer Elements, Genetic–Metabolism ; Gene Expression Regulation–Metabolism ; Glycoprotein Hormones, Alpha Subunit–Metabolism ; Histones–Metabolism ; Mice–Metabolism ; Pituitary Gland–Metabolism ; Promoter Regions, Genetic–Metabolism ; RNA–Metabolism ; RNA, Messenger–Metabolism ; Chromatin ; Glycoprotein Hormones, Alpha Subunit ; Histones ; RNA, Messenger ; RNA ; Chromatin ; Enhancer ; Gonadotropin ; Ncrna ; Pituitary
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descriptionSince the discovery that many transcriptional enhancers are transcribed into long noncoding RNAs termed "enhancer RNAs" (eRNAs), their putative role in enhancer function has been debated. Very recent evidence has indicted that some eRNAs play a role in initiating or activating transcription, possibly by helping recruit and/or stabilize binding of the general transcription machinery to the proximal promoter of their target genes. The distal enhancer of the gonadotropin hormone [alpha]-subunit gene, chorionic gonadotropin alpha (Cga), is responsible for Cga cell-specific expression in gonadotropes and thyrotropes, and we show here that it encodes two bidirectional nonpolyadenylated RNAs whose levels are increased somewhat by exposure to gonadotropin-releasing hormone but are not necessarily linked to Cga transcriptional activity. Knockdown of the more distal eRNA led to a drop in Cga mRNA levels, initially without effect on the forward eRNA levels. With time, however, the repression on the Cga increased, and the forward eRNA levels were suppressed also. We demonstrate that the interaction of the enhancer with the promoter is lost after eRNA knockdown. Dramatic changes also were seen in the chromatin, with an increase in total histone H3 occupancy throughout this region and a virtual loss of histone H3 Lys 4 trimethylation at the promoter following the eRNA knockdown. Moreover, histone H3 Lys 27 (H3K27) acetylation, which was found at both enhancer and promoter in wild-type cells, appeared to have been replaced by H3K27 trimethylation at the enhancer. Thus, the Cga eRNA mediates the physical interaction between these genomic regions and determines the chromatin structure of the proximal promoter to allow gene expression. enhancer | chromatin | ncRNAf | gonadotropin | pituitary
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titleRNA transcribed from a distal enhancer is required for activating the chromatin at the promoter of the gonadotropin α-subunit gene.
authorPnueli, Lilach ; Rudnizky, Sergei ; Yosefzon, Yahav ; Melamed, Philippa
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