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

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 g...

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Main Authors: Laursen, Kristian B., Mongan, Nigel P., Zhuang, Yong, Ng, Mary M., Benoit, Yannick D., Gudas, Lorraine J.
Format: Article
Published: Oxford University Press 2013
Online Access:https://eprints.nottingham.ac.uk/29029/
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author Laursen, Kristian B.
Mongan, Nigel P.
Zhuang, Yong
Ng, Mary M.
Benoit, Yannick D.
Gudas, Lorraine J.
author_facet Laursen, Kristian B.
Mongan, Nigel P.
Zhuang, Yong
Ng, Mary M.
Benoit, Yannick D.
Gudas, Lorraine J.
author_sort Laursen, Kristian B.
building Nottingham Research Data Repository
collection Online Access
description 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.
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spelling nottingham-290292020-05-04T20:19:06Z https://eprints.nottingham.ac.uk/29029/ 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. 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. Oxford University Press 2013-07 Article PeerReviewed Laursen, Kristian B., Mongan, Nigel P., Zhuang, Yong, Ng, Mary M., Benoit, Yannick D. and Gudas, Lorraine J. (2013) Polycomb recruitment attenuates retinoic acid-induced transcription of the bivalent NR2F1 gene. Nucleic acids research, 41 (13). pp. 6430-6443. ISSN 1362-4962 http://nar.oxfordjournals.org/content/41/13/6430 doi:10.1093/nar/gkt367 doi:10.1093/nar/gkt367
spellingShingle Laursen, Kristian B.
Mongan, Nigel P.
Zhuang, Yong
Ng, Mary M.
Benoit, Yannick D.
Gudas, Lorraine J.
Polycomb recruitment attenuates retinoic acid-induced transcription of the bivalent NR2F1 gene
title Polycomb recruitment attenuates retinoic acid-induced transcription of the bivalent NR2F1 gene
title_full Polycomb recruitment attenuates retinoic acid-induced transcription of the bivalent NR2F1 gene
title_fullStr Polycomb recruitment attenuates retinoic acid-induced transcription of the bivalent NR2F1 gene
title_full_unstemmed Polycomb recruitment attenuates retinoic acid-induced transcription of the bivalent NR2F1 gene
title_short Polycomb recruitment attenuates retinoic acid-induced transcription of the bivalent NR2F1 gene
title_sort polycomb recruitment attenuates retinoic acid-induced transcription of the bivalent nr2f1 gene
url https://eprints.nottingham.ac.uk/29029/
https://eprints.nottingham.ac.uk/29029/
https://eprints.nottingham.ac.uk/29029/