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LINT, a novel dL(3)mbt-containing complex, represses malignant brain tumour signature genes.
Meier, Karin Mathieu, Eve-Lyne Finkernagel, Florian Reuter, L Maximilian Scharfe, Maren Doehlemann, Gunther Jarek, Michael Brehm, Alexander
Meier, Karin
Mathieu, Eve-Lyne
Finkernagel, Florian
Reuter, L Maximilian
Scharfe, Maren
Doehlemann, Gunther
Jarek, Michael
Brehm, Alexander
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2012-05
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Abstract
Mutations in the l(3)mbt tumour suppressor result in overproliferation of Drosophila larval brains. Recently, the derepression of different gene classes in l(3)mbt mutants was shown to be causal for transformation. However, the molecular mechanisms of dL(3)mbt-mediated gene repression are not understood. Here, we identify LINT, the major dL(3)mbt complex of Drosophila. LINT has three core subunits-dL(3)mbt, dCoREST, and dLint-1-and is expressed in cell lines, embryos, and larval brain. Using genome-wide ChIP-Seq analysis, we show that dLint-1 binds close to the TSS of tumour-relevant target genes. Depletion of the LINT core subunits results in derepression of these genes. By contrast, histone deacetylase, histone methylase, and histone demethylase activities are not required to maintain repression. Our results support a direct role of LINT in the repression of brain tumour-relevant target genes by restricting promoter access.
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LINT, a novel dL(3)mbt-containing complex, represses malignant brain tumour signature genes. 2012, 8 (5):e1002676 PLoS Genet.
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en
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1553-7404
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