RT Journal Article
SR Electronic
T1 The MLL3/4 complexes and MiDAC co-regulate H4K20ac to control a specific gene expression program
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e202201572
DO 10.26508/lsa.202201572
VO 5
IS 11
A1 Xiaokang Wang
A1 Wojciech Rosikiewicz
A1 Yurii Sedkov
A1 Baisakhi Mondal
A1 Tanner Martinez
A1 Satish Kallappagoudar
A1 Andrey Tvardovskiy
A1 Richa Bajpai
A1 Beisi Xu
A1 Shondra M Pruett-Miller
A1 Robert Schneider
A1 Hans-Martin Herz
YR 2022
UL https://www.life-science-alliance.org/content/5/11/e202201572.abstract
AB 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.