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Distinct CoREST complexes act in a cell-type-specific manner
Igor Mačinković1, Ina Theofel2, Tim Hundertmark2
1Institute of Molecular Biology and Tumor Research, Biomedical Research Center, Philipps-University, Hans-Meerwein-Strasse 2, 35043, Marburg, Germany.
Nucleic Acids Research
|November 9, 2019
Summary
Three distinct CoREST complexes regulate gene expression in a cell-specific manner. These complexes, including dLSD1/CoREST, LINT, and dG9a/CoREST, are crucial for maintaining distinct cell lineages and developmental programs.
Area of Science:
- Epigenetics and Gene Regulation
- Developmental Biology
- Proteomics
Background:
- Co-Repressor of Repressor Element 1-Silencing Transcription factor (CoREST) is a key component of chromatin-modifying complexes.
- Previous studies identified CoREST in transcriptionally repressive complexes, but a comprehensive interactome analysis was lacking.
Purpose of the Study:
- To define the interactomes of two Drosophila CoREST isoforms (dCoREST-L and dCoREST-M).
- To investigate the functional roles of distinct CoREST-containing complexes in different cell types.
Main Methods:
- Proteomic approaches to identify CoREST interactomes in Drosophila.
- Genome-wide chromatin association studies.
- Transcriptome analyses in S2 cells and testes.
Main Results:
- Identified three distinct histone deacetylase complexes: dLSD1/dCoREST, LINT, and dG9a/dCoREST.
- dLSD1/dCoREST complex exclusively uses dCoREST-L, while LINT and dG9a/dCoREST incorporate both isoforms.
- These complexes associate with chromatin at promoters and exhibit lineage-restricted functions.
- In S2 cells, LINT represses germline genes; in testes, dLSD1/dCoREST prevents inappropriate transcription and is vital for spermatogenesis.
Conclusions:
- Uncovered three distinct dCoREST complexes with lineage-restricted roles in gene repression.
- These complexes are essential for maintaining cell-type-specific gene expression programs during development.
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