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Dual role of Med12 in PRC1-dependent gene repression and ncRNA-mediated transcriptional activation.
Cell Cycle. 2016 06 02; 15(11):1479-93.CC

Abstract

Mediator is considered an enhancer of RNA-Polymerase II dependent transcription but its function and regulation in pluripotent mouse embryonic stem cells (mESCs) remains unresolved. One means of controlling the function of Mediator is provided by the binding of the Cdk8 module (Med12, Cdk8, Ccnc and Med13) to the core Mediator. Here we report that Med12 operates together with PRC1 to silence key developmental genes in pluripotency. At the molecular level, while PRC1 represses genes it is also required to assemble ncRNA containing Med12-Mediator complexes. In the course of cellular differentiation the H2A ubiquitin binding protein Zrf1 abrogates PRC1-Med12 binding and facilitates the association of Cdk8 with Mediator. This remodeling of Mediator-associated protein complexes converts Mediator from a transcriptional repressor to a transcriptional enhancer, which then mediates ncRNA-dependent activation of Polycomb target genes. Altogether, our data reveal how the interplay of PRC1, ncRNA and Mediator complexes controls pluripotency and cellular differentiation.

Authors+Show Affiliations

a Laboratory of Molecular Epigenetics, Institute of Molecular Biology (IMB) , Mainz , Germany.a Laboratory of Molecular Epigenetics, Institute of Molecular Biology (IMB) , Mainz , Germany.b Bioinformatics Core Facility, Institute of Molecular Biology (IMB) , Mainz , Germany.a Laboratory of Molecular Epigenetics, Institute of Molecular Biology (IMB) , Mainz , Germany.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27096886

Citation

Papadopoulou, Thaleia, et al. "Dual Role of Med12 in PRC1-dependent Gene Repression and ncRNA-mediated Transcriptional Activation." Cell Cycle (Georgetown, Tex.), vol. 15, no. 11, 2016, pp. 1479-93.
Papadopoulou T, Kaymak A, Sayols S, et al. Dual role of Med12 in PRC1-dependent gene repression and ncRNA-mediated transcriptional activation. Cell Cycle. 2016;15(11):1479-93.
Papadopoulou, T., Kaymak, A., Sayols, S., & Richly, H. (2016). Dual role of Med12 in PRC1-dependent gene repression and ncRNA-mediated transcriptional activation. Cell Cycle (Georgetown, Tex.), 15(11), 1479-93. https://doi.org/10.1080/15384101.2016.1175797
Papadopoulou T, et al. Dual Role of Med12 in PRC1-dependent Gene Repression and ncRNA-mediated Transcriptional Activation. Cell Cycle. 2016 06 2;15(11):1479-93. PubMed PMID: 27096886.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Dual role of Med12 in PRC1-dependent gene repression and ncRNA-mediated transcriptional activation. AU - Papadopoulou,Thaleia, AU - Kaymak,Aysegül, AU - Sayols,Sergi, AU - Richly,Holger, Y1 - 2016/04/20/ PY - 2016/4/21/entrez PY - 2016/4/21/pubmed PY - 2017/5/18/medline KW - Polycomb; Mediator; Cdk8; stem cell; pluripotency; differentiation; Zrf1; ncRNA SP - 1479 EP - 93 JF - Cell cycle (Georgetown, Tex.) JO - Cell Cycle VL - 15 IS - 11 N2 - Mediator is considered an enhancer of RNA-Polymerase II dependent transcription but its function and regulation in pluripotent mouse embryonic stem cells (mESCs) remains unresolved. One means of controlling the function of Mediator is provided by the binding of the Cdk8 module (Med12, Cdk8, Ccnc and Med13) to the core Mediator. Here we report that Med12 operates together with PRC1 to silence key developmental genes in pluripotency. At the molecular level, while PRC1 represses genes it is also required to assemble ncRNA containing Med12-Mediator complexes. In the course of cellular differentiation the H2A ubiquitin binding protein Zrf1 abrogates PRC1-Med12 binding and facilitates the association of Cdk8 with Mediator. This remodeling of Mediator-associated protein complexes converts Mediator from a transcriptional repressor to a transcriptional enhancer, which then mediates ncRNA-dependent activation of Polycomb target genes. Altogether, our data reveal how the interplay of PRC1, ncRNA and Mediator complexes controls pluripotency and cellular differentiation. SN - 1551-4005 UR - https://www.unboundmedicine.com/medline/citation/27096886/Dual_role_of_Med12_in_PRC1_dependent_gene_repression_and_ncRNA_mediated_transcriptional_activation_ L2 - https://www.tandfonline.com/doi/full/10.1080/15384101.2016.1175797 DB - PRIME DP - Unbound Medicine ER -