LINT, a novel dL(3)mbt-containing complex, represses malignant brain tumour signature genes.

PLoS Genetics
Karin MeierAlexander Brehm

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.

References

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Citations

Sep 25, 2014·Proceedings of the National Academy of Sciences of the United States of America·Daniel P BlanchardMichael R Botchan
Dec 9, 2014·Epigenetics : Official Journal of the DNA Methylation Society·Karin Meier, Alexander Brehm
Nov 19, 2013·International Journal of Cancer. Journal International Du Cancer·Julia FeichtingerRamsay J McFarlane
Mar 8, 2018·Development·Rémi-Xavier CouxRuth Lehmann
Nov 9, 2019·Nucleic Acids Research·Igor MačinkovićAlexander Brehm
Jul 31, 2016·Genes & Development·Delphine FagegaltierGregory J Hannon
Nov 21, 2018·Biochemical Genetics·Seyede Zahra Nazari MehrabaniAsaad Azarnezhad
Feb 16, 2020·Nature Communications·Rodrigo G Arzate-MejíaFélix Recillas-Targa
Mar 31, 2019·Scientific Reports·Larisa MelnikovaAnton Golovnin
Nov 17, 2019·Molecular Cell·Karl M GlastadShelley L Berger
Jan 18, 2020·Molecular Cell·Marilyn G Pray-Grant, Patrick A Grant
Jun 13, 2015·Genes & Development·Hyuckjoon KangMitzi I Kuroda

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Methods Mentioned

BETA
ChIP-Seq
gel filtration
ion exchange chromatography
transgenic
ChIPseq
immunoprecipitation
ChIP
affinity purification
Assay
transfection

Software Mentioned

MACS
Image J
Bioconductor
CoREST
dLint
mbt
ClustalW2
gcrma
Ensembl
dCoREST

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