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Polycomb recruitment attenuates retinoic acid–induced transcription of the bivalent NR2F1 gene

Laursen, Kristian B.; Mongan, Nigel P.; Zhuang, Yong; Ng, Mary M.; Benoit, Yannick D.; Gudas, Lorraine J.

Authors

Kristian B. Laursen

Yong Zhuang

Mary M. Ng

Yannick D. Benoit

Lorraine J. Gudas



Abstract

Polycomb proteins play key roles in mediating epigenetic modifications that occur during cell differentiation. The Polycomb repressive complex 2 (PRC2) mediates the tri-methylation of histone H3 lysine 27 (H3K27me3). In this study, we identify a distinguishing feature of two classes of PRC2 target genes, represented by the Nr2F1 (Coup-TF1) and the Hoxa5 gene, respectively. Both genes are transcriptionally activated by all-trans retinoic acid (RA) and display increased levels of the permissive H3K9/K14ac and tri-methylated histone H3 lysine 4 epigenetic marks in response to RA. However, while in response to RA the PRC2 and H3K27me3 marks are greatly decreased at the Hoxa5 promoter, these marks are initially increased at the Nr2F1 promoter. Functional depletion of the essential PRC2 protein Suz12 by short hairpin RNA (shRNA) technology enhanced the RA-associated transcription of Nr2F1, Nr2F2, Meis1, Sox9 and BMP2, but had no effect on the Hoxa5, Hoxa1, Cyp26a1, Cyp26b1 and RARβ2 transcript levels in wild-type embryonic stem cells. We propose that PRC2 recruitment attenuates the RA-associated transcriptional activation of a subset of genes. Such a mechanism would permit the fine-tuning of transcriptional networks during differentiation.

Citation

Laursen, K. B., Mongan, N. P., Zhuang, Y., Ng, M. M., Benoit, Y. D., & Gudas, L. J. (2013). Polycomb recruitment attenuates retinoic acid–induced transcription of the bivalent NR2F1 gene. Nucleic Acids Research, 41(13), 6430–6443. https://doi.org/10.1093/nar/gkt367

Journal Article Type Article
Acceptance Date Apr 17, 2013
Publication Date Jul 1, 2013
Deposit Date Apr 29, 2014
Publicly Available Date Apr 29, 2014
Journal Nucleic Acids Research
Print ISSN 0305-1048
Electronic ISSN 0305-1048
Publisher Oxford University Press
Peer Reviewed Peer Reviewed
Volume 41
Issue 13
Pages 6430–6443
DOI https://doi.org/10.1093/nar/gkt367
Public URL http://eprints.nottingham.ac.uk/id/eprint/3040
Publisher URL http://nar.oxfordjournals.org/content/41/13/6430.full
Copyright Statement Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0

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Publisher Licence URL
http://creativecommons.org/licenses/by/3.0/

Copyright Statement
Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0





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