SUMOylation of the polycomb group protein L3MBTL2 facilitates repression of its target genes.

2.50
Hdl Handle:
http://hdl.handle.net/10033/310975
Title:
SUMOylation of the polycomb group protein L3MBTL2 facilitates repression of its target genes.
Authors:
Stielow, Christina; Stielow, Bastian; Finkernagel, Florian; Scharfe, Maren; Jarek, Michael; Suske, Guntram
Abstract:
Lethal(3) malignant brain tumour like 2 (L3MBTL2) is an integral component of the polycomb repressive complex 1.6 (PRC1.6) and has been implicated in transcriptional repression and chromatin compaction. Here, we show that L3MBTL2 is modified by SUMO2/3 at lysine residues 675 and 700 close to the C-terminus. SUMOylation of L3MBTL2 neither affected its repressive activity in reporter gene assays nor it's binding to histone tails in vitro. In order to analyse whether SUMOylation affects binding of L3MBTL2 to chromatin, we performed ChIP-Seq analysis with chromatin of wild-type HEK293 cells and with chromatin of HEK293 cells stably expressing either FLAG-tagged SUMOylation-competent or SUMOylation-defective L3MBTL2. Wild-type FLAG-L3MBTL2 and the SUMOylation-defective FLAG-L3MBTL2 K675/700R mutant essentially occupied the same sites as endogenous L3MBTL2 suggesting that SUMOylation of L3MBTL2 does not affect chromatin binding. However, a subset of L3MBTL2-target genes, particularly those with low L3MBTL2 occupancy including pro-inflammatory genes, was de-repressed in cells expressing the FLAG-L3MBTL2 K675/700R mutant. Finally, we provide evidence that SUMOylation of L3MBTL2 facilitates repression of these PRC1.6-target genes by balancing the local H2Aub1 levels established by the ubiquitinating enzyme RING2 and the de-ubiquitinating PR-DUB complex.
Citation:
SUMOylation of the polycomb group protein L3MBTL2 facilitates repression of its target genes. 2013: Nucleic Acids Res.
Journal:
Nucleic acids research
Issue Date:
24-Dec-2013
URI:
http://hdl.handle.net/10033/310975
DOI:
10.1093/nar/gkt1317
PubMed ID:
24369422
Type:
Article
ISSN:
1362-4962
Appears in Collections:
publications of the research group genomeanalytics (GMAK)

Full metadata record

DC FieldValue Language
dc.contributor.authorStielow, Christinaen
dc.contributor.authorStielow, Bastianen
dc.contributor.authorFinkernagel, Florianen
dc.contributor.authorScharfe, Marenen
dc.contributor.authorJarek, Michaelen
dc.contributor.authorSuske, Guntramen
dc.date.accessioned2014-01-07T09:44:26Z-
dc.date.available2014-01-07T09:44:26Z-
dc.date.issued2013-12-24-
dc.identifier.citationSUMOylation of the polycomb group protein L3MBTL2 facilitates repression of its target genes. 2013: Nucleic Acids Res.en
dc.identifier.issn1362-4962-
dc.identifier.pmid24369422-
dc.identifier.doi10.1093/nar/gkt1317-
dc.identifier.urihttp://hdl.handle.net/10033/310975-
dc.description.abstractLethal(3) malignant brain tumour like 2 (L3MBTL2) is an integral component of the polycomb repressive complex 1.6 (PRC1.6) and has been implicated in transcriptional repression and chromatin compaction. Here, we show that L3MBTL2 is modified by SUMO2/3 at lysine residues 675 and 700 close to the C-terminus. SUMOylation of L3MBTL2 neither affected its repressive activity in reporter gene assays nor it's binding to histone tails in vitro. In order to analyse whether SUMOylation affects binding of L3MBTL2 to chromatin, we performed ChIP-Seq analysis with chromatin of wild-type HEK293 cells and with chromatin of HEK293 cells stably expressing either FLAG-tagged SUMOylation-competent or SUMOylation-defective L3MBTL2. Wild-type FLAG-L3MBTL2 and the SUMOylation-defective FLAG-L3MBTL2 K675/700R mutant essentially occupied the same sites as endogenous L3MBTL2 suggesting that SUMOylation of L3MBTL2 does not affect chromatin binding. However, a subset of L3MBTL2-target genes, particularly those with low L3MBTL2 occupancy including pro-inflammatory genes, was de-repressed in cells expressing the FLAG-L3MBTL2 K675/700R mutant. Finally, we provide evidence that SUMOylation of L3MBTL2 facilitates repression of these PRC1.6-target genes by balancing the local H2Aub1 levels established by the ubiquitinating enzyme RING2 and the de-ubiquitinating PR-DUB complex.en
dc.languageENG-
dc.rightsArchived with thanks to Nucleic acids researchen
dc.titleSUMOylation of the polycomb group protein L3MBTL2 facilitates repression of its target genes.-
dc.typeArticleen
dc.identifier.journalNucleic acids researchen

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