PXD055009

PXD055009 is an original dataset announced via ProteomeXchange.

Title	Intrinsically Disordered Regions in Chromodomain Helicase DNA-binding (CHD) Proteins Shape Distinct Protein Interaction Networks
Description	Metazoans employ chromodomain helicase DNA-binding (CHD) enzymes to reposition nucleosomal DNA for transcription and replication. The CHD family consists of nine distinct members (CHD1-9) that possess highly conserved chromo and ATPase domains. These domains are flanked by poorly characterised N- and C-termini, which are enriched with intrinsically disordered regions (IDRs) and short aggregation-prone regions (APRs). The contribution of IDRs and APRs to CHD function has remained elusive. In this study we used affinity purification followed by mass spectrometry analysis (AP-MS) to define the protein-protein interaction (PPI) networks within the N- and C-termini of each CHD family member. The results illustrate a comprehensive map of CHD1-9-specific binding proteins that include dozens of novel interactions with transcription regulators and epigenetic factors. Using AlphaFold Multimer we examined the structural predictions of high confidence PPIs from our AP-MS screens and identified APR regions with alpha helical structures that contribute to PPIs. We further investigated a highly conserved APR within the C-terminus of the CHD4 protein and demonstrate that it contributes to the interaction of CHD4 with the nucleosome remodelling and deacetylase (NuRD) and CHD, ADNP, HP1 (ChAHP) complexes. Peptides mimicking this APR effectively disrupt CHD4 binding to both NuRD and ChAHP complexes, consequently triggering the transcriptional activation or repression of hundreds of target genes. Our results emphasise the crucial role that the N- and C-termini of CHD chromatin remodelers play in establishing protein-protein interaction (PPI) networks, which drive unique transcriptional programs.
HostingRepository	PRIDE
AnnounceDate	2025-05-26
AnnouncementXML	Submission_2025-05-25_16:06:59.099.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	mehdi Sharifi tabar
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2024-08-19 17:32:06	ID requested
⏵ 1	2025-05-25 16:06:59	announced

10.1096/fj.202402808rr;

Tabar MS, Parsania C, Giardina C, Feng Y, Wong ACH, Metierre C, Nagarajah R, Dhungel BP, Rasko JEJ, Bailey CG, Intrinsically Disordered Regions Define Unique Protein Interaction Networks in CHD Family Remodelers. FASEB J, 39(10):e70632(2025) [pubmed]

submitter keyword: DNA helicase, chromatin remodelers, transcription, intrinsically disordered regions, aggregation prone regions, protein-protein interactions

Charles G Bailey
contact affiliation	Faculty of Medicine & Health, The University of Sydney, Camperdown, NSW 2006, Australia.
contact email	c.bailey@centenary.org.au
lab head
mehdi Sharifi tabar
contact affiliation	The centenary institute of cancer medicine
contact email	m.tabar@centenary.org.au
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD055009
     1. Label: PRIDE project
     2. Name: Intrinsically Disordered Regions in Chromodomain Helicase DNA-binding (CHD) Proteins Shape Distinct Protein Interaction Networks