Characterization of the nuclear import of the human CHD4-NuRD complex.

Helen Hoffmeister, Simon Holzinger, Marie-Sofie Dürr, Astrid Bruckmann, Susanne Schindler, Regina Gröbner-Ferreira, Reinhard Depping, Gernot Längst

Journal of cell science 2023 Apr 01

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Chromatin remodeling enzymes form large multiprotein complexes that play central roles in regulating access to the genome. Here, we characterize the nuclear import of the human CHD4 protein. We show that CHD4 enters the nucleus by means of several importin-α proteins (1, 5, 6 and 7), but independently of importin β1. Importin α1 directly interacts with a monopartite 'KRKR'-motif in the N-terminus of CHD4 (amino acids 304-307). However, alanine mutagenesis of this motif only leads to an ∼50% reduction in nuclear localization of CHD4, implying that there are additional import mechanisms. Interestingly, we could show that CHD4 was already associated with the nucleosome remodeling deacetylase (NuRD) core subunits, such as MTA2, HDAC1 and RbAp46 (also known as RBBP7), in the cytoplasm, suggesting an assembly of the NuRD core complex before nuclear import. We propose that, in addition to the importin-α-dependent nuclear localization signal, CHD4 is dragged into the nucleus by a 'piggyback' mechanism using the import signals of the associated NuRD subunits. © 2023. Published by The Company of Biologists Ltd.

Citation

Helen Hoffmeister, Simon Holzinger, Marie-Sofie Dürr, Astrid Bruckmann, Susanne Schindler, Regina Gröbner-Ferreira, Reinhard Depping, Gernot Längst. Characterization of the nuclear import of the human CHD4-NuRD complex. Journal of cell science. 2023 Apr 01;136(7)