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Nucleic Acids Res. 2019 Dec 16;47(22):11649-11666. doi: 10.1093/nar/gkz1050.

Distinct CoREST complexes act in a cell-type-specific manner.

Author information

1
Institute of Molecular Biology and Tumor Research, Biomedical Research Center, Philipps-University, Hans-Meerwein-Strasse 2, 35043, Marburg, Germany.
2
Department of Biology, Philipps-University, Karl-von-Frisch-Strasse 8, 35043, Marburg, Germany.
3
Protein Analysis Unit, BioMedical Center, Faculty of Medicine, Ludwig-Maximilians-University Munich, Großhadernerstrasse 9, 82152 Martinsried, Germany.
4
Genomics Core Facility, Institute of Molecular Oncology, Philipps-University, Hans-Meerwein-Strasse 3, 35043 Marburg, Germany.

Abstract

CoREST has been identified as a subunit of several protein complexes that generate transcriptionally repressive chromatin structures during development. However, a comprehensive analysis of the CoREST interactome has not been carried out. We use proteomic approaches to define the interactomes of two dCoREST isoforms, dCoREST-L and dCoREST-M, in Drosophila. We identify three distinct histone deacetylase complexes built around a common dCoREST/dRPD3 core: A dLSD1/dCoREST complex, the LINT complex and a dG9a/dCoREST complex. The latter two complexes can incorporate both dCoREST isoforms. By contrast, the dLSD1/dCoREST complex exclusively assembles with the dCoREST-L isoform. Genome-wide studies show that the three dCoREST complexes associate with chromatin predominantly at promoters. Transcriptome analyses in S2 cells and testes reveal that different cell lineages utilize distinct dCoREST complexes to maintain cell-type-specific gene expression programmes: In macrophage-like S2 cells, LINT represses germ line-related genes whereas other dCoREST complexes are largely dispensable. By contrast, in testes, the dLSD1/dCoREST complex prevents transcription of germ line-inappropriate genes and is essential for spermatogenesis and fertility, whereas depletion of other dCoREST complexes has no effect. Our study uncovers three distinct dCoREST complexes that function in a lineage-restricted fashion to repress specific sets of genes thereby maintaining cell-type-specific gene expression programmes.

PMID:
31701127
DOI:
10.1093/nar/gkz1050

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