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Schwartz, Yuri B.
Publications (3 of 3) Show all publications
Kahn, T. G., Dorafshan, E., Schultheis, D., Zare, A., Stenberg, P., Reim, I., . . . Schwartz, Y. B. (2016). Interdependence of PRC1 and PRC2 for recruitment to Polycomb Response Elements. Nucleic Acids Research, 44(21), 10132-10149
Open this publication in new window or tab >>Interdependence of PRC1 and PRC2 for recruitment to Polycomb Response Elements
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2016 (English)In: Nucleic Acids Research, ISSN 0305-1048, E-ISSN 1362-4962, Vol. 44, no 21, p. 10132-10149Article in journal (Refereed) Published
Abstract [en]

Polycomb Group (PcG) proteins are epigenetic repressors essential for control of development and cell differentiation. They form multiple complexes of which PRC1 and PRC2 are evolutionary conserved and obligatory for repression. The targeting of PRC1 and PRC2 is poorly understood and was proposed to be hierarchical and involve tri-methylation of histone H3 (H3K27me3) and/or monoubiquitylation of histone H2A (H2AK118ub). Here, we present a strict test of this hypothesis using the Drosophila model. We discover that neither H3K27me3 nor H2AK118ub is required for targeting PRC complexes to Polycomb Response Elements (PREs). We find that PRC1 can bind PREs in the absence of PRC2 but at many PREs PRC2 requires PRC1 to be targeted. We show that one role of H3K27me3 is to allow PcG complexes anchored at PREs to interact with surrounding chromatin. In contrast, the bulk of H2AK118ub is unrelated to PcG repression. These findings radically change our view of how PcG repression is targeted and suggest that PRC1 and PRC2 can communicate independently of histone modifications.

Keywords
Epigenetics, Gene regulation, Polycomb repression mechanisms, Polycomb Response Elements
National Category
Genetics Biochemistry and Molecular Biology
Research subject
Genetics; Molecular Biology
Identifiers
urn:nbn:se:umu:diva-128511 (URN)10.1093/nar/gkw701 (DOI)000393979400015 ()27557709 (PubMedID)
Available from: 2016-12-06 Created: 2016-12-06 Last updated: 2018-11-19Bibliographically approved
Dorafshan, E., Kahn, T. G., Glotov, A., Savitsky, M., Walther, M., Reuter, G. & Schwartz, Y. B.Does Ash1 counteract Polycomb repression by methylating H3K36?.
Open this publication in new window or tab >>Does Ash1 counteract Polycomb repression by methylating H3K36?
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(English)Manuscript (preprint) (Other academic)
Abstract [en]

Polycomb repression is critical to maintain cell type specific genome expression programs in a wide range of multicellular animals. Equally important but less studied is the Trithorax group system, which safeguards Polycomb target genes from the repression in cells where they have to remain active. Based on in vitro studies it was proposed that the Trithorax group system acts via methylation of histone H3 at Lysine 4 (H3K4) and Lysine 36 (H3K36) thereby inhibiting histone methyltransferase activity of the Polycomb complexes. This hypothesis is yet to be comprehensively tested in vivo. Here we used the power of the Drosophila model to investigate how the Trithorax group protein Ash1 and the H3K36 methylation counteract Polycomb repression. We show, for the first time, that Ash1 is the only Drosophila H3K36-specific methyltransferase required to prevent excessive Polycomb repression of homeotic genes. Unexpectedly, our experiments revealed no correlation between the extent of H3K36 methylation and the resistance to Polycomb repression. Furthermore, we find that complete substitution of the zygotic histone H3 with a variant in which Lysine 36 is replaced by Arginine does not cause excessive repression of Drosophila homeotic genes. Together with earlier studies, our results suggest that the model, where the Trithorax group proteins methylate histone H3 to inhibit the histone methyltransferase activity of the Polycomb complexes, may need to be reevaluated.

Keywords
Polycomb, H3K36 methylation, HOX genes, Trithorax, Ash1, Drosophila
National Category
Genetics Developmental Biology
Research subject
Molecular Biology; Genetics
Identifiers
urn:nbn:se:umu:diva-153350 (URN)
Funder
Knut and Alice Wallenberg FoundationSwedish Research CouncilThe Kempe Foundations
Available from: 2018-11-19 Created: 2018-11-19 Last updated: 2018-11-20
Dorafshan, E., Kahn, T. G., Glotov, A., Savitsky, M. & Schwartz, Y. B.Functional dissection of Drosophila Ash1 domains.
Open this publication in new window or tab >>Functional dissection of Drosophila Ash1 domains
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(English)Manuscript (preprint) (Other academic)
Keywords
Ash1, Ash1 domains, PHD, SET, BAH, AT hooks, novel alleles
National Category
Genetics
Research subject
Molecular Biology; Genetics
Identifiers
urn:nbn:se:umu:diva-153352 (URN)
Funder
Swedish Research CouncilKnut and Alice Wallenberg FoundationThe Kempe Foundations
Available from: 2018-11-19 Created: 2018-11-19 Last updated: 2018-11-20
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