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Wang, X. ; Rosikiewicz, W.* ; Sedkov, Y.* ; Mondal, B.* ; Martinez, T.* ; Kallappagoudar, S.* ; Tvardovskiy, A. ; Bajpai, R.* ; Xu, B.* ; Pruett-Miller, S.M.* ; Schneider, R. ; Herz, H.M.*

The MLL3/4 complexes and MiDAC co-regulate H4K20ac to control a specific gene expression program.

Life Sci. All. 5:e202201572 (2022)
Publ. Version/Full Text DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
The mitotic deacetylase complex MiDAC has recently been shown to play a vital physiological role in embryonic development and neurite outgrowth. However, how MiDAC functionally intersects with other chromatin-modifying regulators is poorly understood. Here, we describe a physical interaction between the histone H3K27 demethylase UTX, a complex-specific subunit of the enhancer-associated MLL3/4 complexes, and MiDAC. We demonstrate that UTX bridges the association of the MLL3/4 complexes and MiDAC by interacting with ELMSAN1, a scaffolding subunit of MiDAC. Our data suggest that MiDAC constitutes a negative genome-wide regulator of H4K20ac, an activity which is counteracted by the MLL3/4 complexes. MiDAC and the MLL3/4 complexes co-localize at many genomic regions, which are enriched for H4K20ac and the enhancer marks H3K4me1, H3K4me2, and H3K27ac. We find that MiDAC antagonizes the recruitment of UTX and MLL4 and negatively regulates H4K20ac, and to a lesser extent H3K4me2 and H3K27ac, resulting in transcriptional attenuation of associated genes. In summary, our findings provide a paradigm how the opposing roles of chromatin-modifying components, such as MiDAC and the MLL3/4 complexes, balance the transcriptional output of specific gene expression programs.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
ISSN (print) / ISBN 2575-1077
e-ISSN 2575-1077
Quellenangaben Volume: 5, Issue: 11, Pages: , Article Number: e202201572 Supplement: ,
Publisher EMBO Press
Publishing Place Heidelberg
Non-patent literature Publications
Reviewing status Peer reviewed
Grants American Lebanese Syrian Associated Charities
National Cancer Institute
National Institutes of Health