PXD060154-1

PXD060154 is an original dataset announced via ProteomeXchange.

Title	The six unique histone deacetylase (HDAC) 1 complexes vary greatly in abundance and utilize distinct molecular assemblies.
Description	Histone deacetylase 1 and 2 (HDAC1/2) are highly related enzymes that that regulate histone acetylation levels in all cells, as catalytic and structural components of six unique multi-protein complexes: SIN3, NuRD, CoREST, MIDAC, MIER1 and RERE. Co-immunoprecipitation of HDAC1-Flag followed by mass-spectrometry revealed that 92% of the HDAC1 in mouse embryonic stem cells resides in 3 complexes, NuRD (49%), CoREST (28%) and SIN3 (15%). To delineate the function of these different biochemical entities we compared binary structures of the MTA1:HDAC1 and MIDAC:HDAC1 to identify conserved residues on the surface of HDAC1 that would potentially perturb one or more complexes. A single mutation, Y48E, disrupts binding to all complexes with the exception of SIN3. Remarkably, rescue experiments performed with HDAC1-Y48E in HDAC1/2 double-knockout cells, showed that retention of SIN3 binding alone is sufficient for cell viability. Gene expression and histone acetylation patterns were perturbed in both Y48E and a second mutant cell line, HDAC1-E63R, indicating that cells require a full repertoire of the HDAC1/2 complexes to regulate their transcriptome appropriately. Comparative analysis of SIN3/HDAC1 and MTA1/HDAC1 structures confirmed the differential modes of HDAC1 recruitment, with the surface including Y48 bound only by ELM2/SANT domain containing complexes. We provide novel molecular insights into the abundance, co-factors and assemblies of this crucial family of chromatin modifying machines.
HostingRepository	PRIDE
AnnounceDate	2025-08-22
AnnouncementXML	Submission_2025-08-22_02:39:36.426.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Mark Collins
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2025-01-24 06:05:04	ID requested
⏵ 1	2025-08-22 02:39:36	announced

Dataset with its publication pending

submitter keyword: acetylation,HDAC1, protein complex, chromation modification

Mark Collins
contact affiliation	School of Biosciences Firth Court, Western Bank University of Sheffield Sheffield, S10 2TN United Kingdom
contact email	mark.collins@sheffield.ac.uk
lab head
Mark Collins
contact affiliation	University of Sheffield
contact email	mark.collins@sheffield.ac.uk
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2025/08/PXD060154

PRIDE project URI

• PRIDE
  1. PXD060154
     1. Label: PRIDE project
     2. Name: The six unique histone deacetylase (HDAC) 1 complexes vary greatly in abundance and utilize distinct molecular assemblies.