Intragenic enhancers act as alternative promoters

Monika S Kowalczyk; Jim R Hughes; David Garrick; Magnus D Lynch; Jacqueline A Sharpe; Jacqueline A Sloane-Stanley; Simon J McGowan; Marco De Gobbi; Mona Hosseini; Douglas Vernimmen; Jill M Brown; Nicola E Gray; Licio Collavin; Richard J Gibbons; Jonathan Flint; Stephen Taylor; Veronica J Buckle; Thomas A Milne; William G Wood; Douglas R Higgs

doi:10.1016/j.molcel.2011.12.021

Intragenic enhancers act as alternative promoters

Monika S Kowalczyk, Jim R Hughes, David Garrick, Magnus D Lynch, Jacqueline A Sharpe, Jacqueline A Sloane-Stanley, Simon J McGowan, Marco De Gobbi, Mona Hosseini, Douglas Vernimmen, Jill M Brown, Nicola E Gray, Licio Collavin, Richard J Gibbons, Jonathan Flint, Stephen Taylor, Veronica J Buckle, Thomas A Milne, William G Wood, Douglas R Higgs

Royal (Dick) School of Veterinary Studies

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

Abstract / Description of output

A substantial amount of organismal complexity is thought to be encoded by enhancers which specify the location, timing, and levels of gene expression. In mammals there are more enhancers than promoters which are distributed both between and within genes. Here we show that activated, intragenic enhancers frequently act as alternative tissue-specific promoters producing a class of abundant, spliced, multiexonic poly(A)(+) RNAs (meRNAs) which reflect the host gene's structure. meRNAs make a substantial and unanticipated contribution to the complexity of the transcriptome, appearing as alternative isoforms of the host gene. The low protein-coding potential of meRNAs suggests that many meRNAs may be byproducts of enhancer activation or underlie as-yet-unidentified RNA-encoded functions. Distinguishing between meRNAs and mRNAs will transform our interpretation of dynamic changes in transcription both at the level of individual genes and of the genome as a whole.

Original language	English
Pages (from-to)	447-58
Number of pages	12
Journal	Molecular Cell
Volume	45
Issue number	4
DOIs	https://doi.org/10.1016/j.molcel.2011.12.021
Publication status	Published - 2012

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Kowalczyk, M. S., Hughes, J. R., Garrick, D., Lynch, M. D., Sharpe, J. A., Sloane-Stanley, J. A., McGowan, S. J., De Gobbi, M., Hosseini, M., Vernimmen, D., Brown, J. M., Gray, N. E., Collavin, L., Gibbons, R. J., Flint, J., Taylor, S., Buckle, V. J., Milne, T. A., Wood, W. G., & Higgs, D. R. (2012). Intragenic enhancers act as alternative promoters. Molecular Cell, 45(4), 447-58. https://doi.org/10.1016/j.molcel.2011.12.021

@article{78ef6102cc1f4946a0dedd267c2d978f,

title = "Intragenic enhancers act as alternative promoters",

abstract = "A substantial amount of organismal complexity is thought to be encoded by enhancers which specify the location, timing, and levels of gene expression. In mammals there are more enhancers than promoters which are distributed both between and within genes. Here we show that activated, intragenic enhancers frequently act as alternative tissue-specific promoters producing a class of abundant, spliced, multiexonic poly(A)(+) RNAs (meRNAs) which reflect the host gene's structure. meRNAs make a substantial and unanticipated contribution to the complexity of the transcriptome, appearing as alternative isoforms of the host gene. The low protein-coding potential of meRNAs suggests that many meRNAs may be byproducts of enhancer activation or underlie as-yet-unidentified RNA-encoded functions. Distinguishing between meRNAs and mRNAs will transform our interpretation of dynamic changes in transcription both at the level of individual genes and of the genome as a whole.",

author = "Kowalczyk, {Monika S} and Hughes, {Jim R} and David Garrick and Lynch, {Magnus D} and Sharpe, {Jacqueline A} and Sloane-Stanley, {Jacqueline A} and McGowan, {Simon J} and {De Gobbi}, Marco and Mona Hosseini and Douglas Vernimmen and Brown, {Jill M} and Gray, {Nicola E} and Licio Collavin and Gibbons, {Richard J} and Jonathan Flint and Stephen Taylor and Buckle, {Veronica J} and Milne, {Thomas A} and Wood, {William G} and Higgs, {Douglas R}",

year = "2012",

doi = "10.1016/j.molcel.2011.12.021",

language = "English",

volume = "45",

pages = "447--58",

journal = "Molecular Cell",

issn = "1097-2765",

publisher = "Cell Press",

number = "4",

}

Kowalczyk, MS, Hughes, JR, Garrick, D, Lynch, MD, Sharpe, JA, Sloane-Stanley, JA, McGowan, SJ, De Gobbi, M, Hosseini, M, Vernimmen, D, Brown, JM, Gray, NE, Collavin, L, Gibbons, RJ, Flint, J, Taylor, S, Buckle, VJ, Milne, TA, Wood, WG & Higgs, DR 2012, 'Intragenic enhancers act as alternative promoters', Molecular Cell, vol. 45, no. 4, pp. 447-58. https://doi.org/10.1016/j.molcel.2011.12.021

TY - JOUR

T1 - Intragenic enhancers act as alternative promoters

AU - Kowalczyk, Monika S

AU - Hughes, Jim R

AU - Garrick, David

AU - Lynch, Magnus D

AU - Sharpe, Jacqueline A

AU - Sloane-Stanley, Jacqueline A

AU - McGowan, Simon J

AU - De Gobbi, Marco

AU - Hosseini, Mona

AU - Vernimmen, Douglas

AU - Brown, Jill M

AU - Gray, Nicola E

AU - Collavin, Licio

AU - Gibbons, Richard J

AU - Flint, Jonathan

AU - Taylor, Stephen

AU - Buckle, Veronica J

AU - Milne, Thomas A

AU - Wood, William G

AU - Higgs, Douglas R

PY - 2012

Y1 - 2012

N2 - A substantial amount of organismal complexity is thought to be encoded by enhancers which specify the location, timing, and levels of gene expression. In mammals there are more enhancers than promoters which are distributed both between and within genes. Here we show that activated, intragenic enhancers frequently act as alternative tissue-specific promoters producing a class of abundant, spliced, multiexonic poly(A)(+) RNAs (meRNAs) which reflect the host gene's structure. meRNAs make a substantial and unanticipated contribution to the complexity of the transcriptome, appearing as alternative isoforms of the host gene. The low protein-coding potential of meRNAs suggests that many meRNAs may be byproducts of enhancer activation or underlie as-yet-unidentified RNA-encoded functions. Distinguishing between meRNAs and mRNAs will transform our interpretation of dynamic changes in transcription both at the level of individual genes and of the genome as a whole.

AB - A substantial amount of organismal complexity is thought to be encoded by enhancers which specify the location, timing, and levels of gene expression. In mammals there are more enhancers than promoters which are distributed both between and within genes. Here we show that activated, intragenic enhancers frequently act as alternative tissue-specific promoters producing a class of abundant, spliced, multiexonic poly(A)(+) RNAs (meRNAs) which reflect the host gene's structure. meRNAs make a substantial and unanticipated contribution to the complexity of the transcriptome, appearing as alternative isoforms of the host gene. The low protein-coding potential of meRNAs suggests that many meRNAs may be byproducts of enhancer activation or underlie as-yet-unidentified RNA-encoded functions. Distinguishing between meRNAs and mRNAs will transform our interpretation of dynamic changes in transcription both at the level of individual genes and of the genome as a whole.

U2 - 10.1016/j.molcel.2011.12.021

DO - 10.1016/j.molcel.2011.12.021

M3 - Article

C2 - 22264824

SN - 1097-2765

VL - 45

SP - 447

EP - 458

JO - Molecular Cell

JF - Molecular Cell

IS - 4

ER -

Intragenic enhancers act as alternative promoters

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