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

Hoffmeister, Helen and Holzinger, Simon and Duerr, Marie-Sofie and Bruckmann, Astrid and Schindler, Susanne and Groebner-Ferreira, Regina and Depping, Reinhard and Laengst, Gernot (2023) Characterization of the nuclear import of the human CHD4-NuRD complex. JOURNAL OF CELL SCIENCE, 136 (7): jcs260724. ISSN 0021-9533, 1477-9137

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Abstract

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-alpha proteins (1, 5, 6 and 7), but independently of importin beta 1. Importin alpha 1 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 similar to 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-alpha-dependent nuclear localization signal, CHD4 is dragged into the nucleus by a 'piggyback' mechanism using the import signals of the associated NuRD subunits.

Item Type: Article
Uncontrolled Keywords: HUMAN PROTEIN ATLAS; LOCALIZATION SIGNAL; DEACETYLASE COMPLEX; BINDING; IDENTIFICATION; ALPHA; TRANSPORT; CHROMATIN; SEQUENCE; NURD; NuRD; Chromatin remodeling; Nuclear import
Subjects: 500 Science > 570 Life sciences
Divisions: Biology, Preclinical Medicine > Institut für Biochemie, Genetik und Mikrobiologie > Lehrstuhl für Biochemie I > Prof. Dr. Gunter Meister
Biology, Preclinical Medicine > Institut für Biochemie, Genetik und Mikrobiologie > Lehrstuhl für Biochemie III > Prof. Dr. Gernot Längst
Depositing User: Dr. Gernot Deinzer
Date Deposited: 09 Mar 2024 13:31
Last Modified: 09 Mar 2024 13:32
URI: https://pred.uni-regensburg.de/id/eprint/59378

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