Intrinsically Disordered Regions Define Unique Protein Interaction Networks in CHD Family Remodelers

Tabar, M. S.; Parsania, C.; Giardina, C.; Feng, Y.; Wong, A. C.; metierre, C.; Nagarajah, R.; Dhungel, B. P.; Rasko, J. E.; Bailey, C. G.

doi:10.1101/2024.08.25.609601

bioRxiv · 10.1101/2024.08.25.609601

Intrinsically Disordered Regions Define Unique Protein Interaction Networks in CHD Family Remodelers

Tabar, M. S.·Parsania, C.·Giardina, C.·Feng, Y.·Wong, A. C.·metierre, C.·Nagarajah, R.·Dhungel, B. P.·Rasko, J. E.·Bailey, C. G.

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Abstract

Chromodomain helicase DNA-binding (CHD1-9) enzymes reposition nucleosomal DNA for transcription, recombination, and replication. They possess highly conserved ATPase domains flanked by poorly characterised N- and C-termini, which are enriched with intrinsically disordered regions (IDRs) and short aggregation-prone regions (APRs). The roles of IDRs and APRs in CHD function has remained elusive. Here, by integrating proteomics and AlphaFold Multimer analysis, we defined the protein-protein interaction (PPI) networks within the N- and C-termini of all CHDs. We generated a comprehensive map of CHD1-9-specific binding proteins, revealing dozens of novel interactions with transcription regulators. We identified APR regions that contribute to PPI formation and demonstrated that a highly conserved APR within the C-terminus of CHD4 is critical for its interaction with the nucleosome remodeling and deacetylase (NuRD), as well as the CHD, ADNP, and HP1 (ChAHP) complexes. Further analysis unravels a regulatory role for the CHD4 APR in gene transcription during erythrocyte formation. Our results emphasize that the N- and C-termini of CHD chromatin remodelers establish PPI networks that drive unique transcriptional programs.

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Tabar, M. S., Parsania, C., Giardina, C., Feng, Y., Wong, A. C., metierre, C., Nagarajah, R., Dhungel, B. P., Rasko, J. E., Bailey, C. G.. 2024-08-25. Intrinsically Disordered Regions Define Unique Protein Interaction Networks in CHD Family Remodelers. https://doi.org/10.1101/2024.08.25.609601

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