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Boosting transcription by transcription: enhancer-associated transcripts

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Abstract

Enhancers are traditionally viewed as DNA sequences located some distance from a promoter that act in cis and in an orientation-independent fashion to increase utilization of specific promoters and thereby regulate gene expression. Much progress has been made over the last decade toward understanding how these distant elements interact with target promoters, but how transcription is enhanced remains an object of active inquiry. Recent reports convey the prevalence and diversity of enhancer transcription and transcripts and support both as key factors with mechanistically distinct, but not mutually exclusive roles in enhancer function. Decoupling the causes and effects of transcription on the local chromatin landscape and understanding the role of enhancer transcripts in the context of long-range interactions are challenges that require additional attention. In this review, we focus on the possible functions of enhancer transcription by highlighting several recent enhancer RNA papers and, within the context of other enhancer studies, speculate on the role of enhancer transcription in regulating differential gene expression.

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Abbreviations

AR:

Androgen receptor

Arc:

Activity-regulated cytoskeleton-associated protein

CBP:

CREB-binding protein

ChIP:

Chromatin immunoprecipitation

ChIP-seq:

ChIP coupled with massively paralleled sequencing

E2:

17β-Estradiol

ER-α:

Estrogen receptor-α

eRNA:

Enhancer RNA

GRO-seq:

Global run-on sequencing

H3K9ac:

Histone H3 acetylated at lysine 9

H3K27ac:

Histone H3 acetylated at lysine 27

H3K4me1:

Histone H3 monomethylated at lysine 4

H3K4me2:

Histone H3 dimethylated at lysine 4

H3K4me3:

Histone H3 trimethylated at lysine 4

H3K36me3:

Histone H3 trimethylated at lysine 36

H3S10ph:

H3 serine-10 phosphorylation

HAT:

Histone acetyltransferase

HDAC:

Histone deacetylase

kb:

Kilobase

KCl:

Potassium chloride

KLA:

Kdo2-lipid A

LNA:

Locked nucleic acids

lncRNA:

Long noncoding RNA

LPS:

Lipopolysaccharide

ncRNA-a:

Noncoding RNA-activating

NPAS4:

Neuronal PAS domain 4

Pol II:

RNA polymerase II

RNA-seq:

Massively parallel RNA sequencing

SRF:

Serum response factor

siRNA:

Small interfering RNA

TF:

Transcription factor

TLR4:

Toll-like receptor 4

TSS:

Transcription start sites

TTX:

Tetrodotoxin

3C:

Chromosome conformation capture

3D-DSL:

Three-dimensional DNA selection and ligation

4C:

Circularized chromosome conformation capture

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Acknowledgments

The authors apologize to those whose work is not cited due to space limitations. This work was supported by the National Institutes of Health [GM073120 and NS080779 to B.P.C].

Conflict of interest

The authors declare they have no conflicts of interest.

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Authors and Affiliations

  1. Department of Biological Science, Florida State University, 319 Stadium Drive, King Building 3076, Tallahassee, FL, 32306-4295, USA

    Emily M. Darrow & Brian P. Chadwick

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  1. Emily M. Darrow
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  2. Brian P. Chadwick
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Correspondence to Brian P. Chadwick.

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Responsible Editor: Brian P. Chadwick, Kristin C. Scott, and Beth A. Sullivan

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Darrow, E.M., Chadwick, B.P. Boosting transcription by transcription: enhancer-associated transcripts. Chromosome Res 21, 713–724 (2013). https://doi.org/10.1007/s10577-013-9384-6

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