Bidirectional transcription initiation marks accessible chromatin and is not specific to enhancers

Robert S. Young; Yatendra Kumar; Wendy A. Bickmore; Martin S. Taylor

doi:10.1186/s13059-017-1379-8

Bidirectional transcription initiation marks accessible chromatin and is not specific to enhancers

Robert S. Young, Yatendra Kumar, Wendy A. Bickmore, Martin S. Taylor

Research output: Contribution to journal › Article › peer-review

Abstract

Background: Enhancers are modular regulatory elements that are central to the spatial and temporal regulation of gene expression. Bidirectional transcription initiating at enhancers has been proposed to mark active enhancers and as such has been utilized to experimentally identify active enhancers de novo.

Results: Here, we show that bidirectional transcription initiation is a pervasive feature of accessible chromatin, including at enhancers, promoters, and other DNase hypersensitive regions not marked with canonical histone modification profiles. Transcription is less predictive for enhancer activity than epigenetic modifications such as H3K4me1 or the accessibility of DNA when measured both in enhancer assays and at endogenous loci. The stability of enhancer initiated transcripts does not influence measures of enhancer activity and we cannot detect evidence of purifying selection on the resulting enhancer RNAs within the human population.

Conclusions: Our results indicate that bidirectional transcription initiation from accessible chromatin is not sufficient for, nor specific to, enhancer activity. Transcription initiating at enhancers may be a frequent by-product of promiscuous RNA polymerase initiation at accessible chromatin and is unlikely to generally play a functional role in enhancer activity.

Original language	English
Article number	242
Number of pages	11
Journal	Genome Biology
Volume	18
DOIs	https://doi.org/10.1186/s13059-017-1379-8
Publication status	Published - 28 Dec 2017

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2 Finished

HGU Core Award Apr 12 - MAr 18
Hastie, N. (Principal Investigator), Adams, I. (Co-investigator), Baldock, R. (Co-investigator), Bickmore, W. (Co-investigator), Caceres, J. (Co-investigator), Dorin, J. (Co-investigator), FitzPatrick, D. (Co-investigator), Haley, C. (Co-investigator), Hill, B. (Co-investigator), Jackson, I. (Co-investigator), Jackson, A. (Co-investigator), Kudla, G. (Co-investigator), Meehan, R. (Co-investigator) & Patton, E. (Co-investigator)
MRC
1/04/12 → 31/03/18
Project: Research
The role of spatial nuclear organisation in genome function
Bickmore, W. (Principal Investigator)
1/04/12 → 31/03/18
Project: Research

1 Preprint

Bidirectional transcription marks accessible chromatin and is not specific to enhancers
Young, R. S., Kumar, Y., Bickmore, W. A. & Taylor, M. S., 13 Apr 2016, bioRxiv.
Research output: Working paper › Preprint

Bidirectional transcription initiation marks accessible chromatin and is not specific to enhancers
Young, R. (Creator) & Taylor, M. (Creator), Edinburgh DataShare, 21 Dec 2017
DOI: 10.7488/ds/2266
Dataset

Martin Taylor
- MRC Human Genetics Unit
- Institute of Genetics and Cancer - Personal Chair of Evolutionary Genomics
- Institute of Genetics and Cancer
Person: Academic: Research Active
Rob Young
- Edinburgh Medical School - Senior Lecturer
Person: Academic: Research Active (Research Assistant)

Cite this

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title = "Bidirectional transcription initiation marks accessible chromatin and is not specific to enhancers",

abstract = "Background: Enhancers are modular regulatory elements that are central to the spatial and temporal regulation of gene expression. Bidirectional transcription initiating at enhancers has been proposed to mark active enhancers and as such has been utilized to experimentally identify active enhancers de novo. Results: Here, we show that bidirectional transcription initiation is a pervasive feature of accessible chromatin, including at enhancers, promoters, and other DNase hypersensitive regions not marked with canonical histone modification profiles. Transcription is less predictive for enhancer activity than epigenetic modifications such as H3K4me1 or the accessibility of DNA when measured both in enhancer assays and at endogenous loci. The stability of enhancer initiated transcripts does not influence measures of enhancer activity and we cannot detect evidence of purifying selection on the resulting enhancer RNAs within the human population. Conclusions: Our results indicate that bidirectional transcription initiation from accessible chromatin is not sufficient for, nor specific to, enhancer activity. Transcription initiating at enhancers may be a frequent by-product of promiscuous RNA polymerase initiation at accessible chromatin and is unlikely to generally play a functional role in enhancer activity.",

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language = "English",

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Y1 - 2017/12/28

N2 - Background: Enhancers are modular regulatory elements that are central to the spatial and temporal regulation of gene expression. Bidirectional transcription initiating at enhancers has been proposed to mark active enhancers and as such has been utilized to experimentally identify active enhancers de novo. Results: Here, we show that bidirectional transcription initiation is a pervasive feature of accessible chromatin, including at enhancers, promoters, and other DNase hypersensitive regions not marked with canonical histone modification profiles. Transcription is less predictive for enhancer activity than epigenetic modifications such as H3K4me1 or the accessibility of DNA when measured both in enhancer assays and at endogenous loci. The stability of enhancer initiated transcripts does not influence measures of enhancer activity and we cannot detect evidence of purifying selection on the resulting enhancer RNAs within the human population. Conclusions: Our results indicate that bidirectional transcription initiation from accessible chromatin is not sufficient for, nor specific to, enhancer activity. Transcription initiating at enhancers may be a frequent by-product of promiscuous RNA polymerase initiation at accessible chromatin and is unlikely to generally play a functional role in enhancer activity.

AB - Background: Enhancers are modular regulatory elements that are central to the spatial and temporal regulation of gene expression. Bidirectional transcription initiating at enhancers has been proposed to mark active enhancers and as such has been utilized to experimentally identify active enhancers de novo. Results: Here, we show that bidirectional transcription initiation is a pervasive feature of accessible chromatin, including at enhancers, promoters, and other DNase hypersensitive regions not marked with canonical histone modification profiles. Transcription is less predictive for enhancer activity than epigenetic modifications such as H3K4me1 or the accessibility of DNA when measured both in enhancer assays and at endogenous loci. The stability of enhancer initiated transcripts does not influence measures of enhancer activity and we cannot detect evidence of purifying selection on the resulting enhancer RNAs within the human population. Conclusions: Our results indicate that bidirectional transcription initiation from accessible chromatin is not sufficient for, nor specific to, enhancer activity. Transcription initiating at enhancers may be a frequent by-product of promiscuous RNA polymerase initiation at accessible chromatin and is unlikely to generally play a functional role in enhancer activity.

U2 - 10.1186/s13059-017-1379-8

DO - 10.1186/s13059-017-1379-8

M3 - Article

SN - 1465-6906

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JO - Genome Biology

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ER -

Bidirectional transcription initiation marks accessible chromatin and is not specific to enhancers

Abstract

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Projects

HGU Core Award Apr 12 - MAr 18

The role of spatial nuclear organisation in genome function

Research output

Bidirectional transcription marks accessible chromatin and is not specific to enhancers

Datasets

Bidirectional transcription initiation marks accessible chromatin and is not specific to enhancers

Profiles

Martin Taylor

Rob Young

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