PXD062956-1

PXD062956 is an original dataset announced via ProteomeXchange.

Title	Histone variant H2A.Z enhances histone and nucleosome dynamics
Description	Interchanging canonical histone H2A with variant H2A.Z in chromatin complexes is vital for the proper regulation of transcription, DNA damage repair, and centromere maintenance. However, the physical mechanisms underlying functional differences between H2A and H2A.Z complexes are unclear. Human H2A and H2A.Z have a high degree of sequence and structural conservation, with subtle differences occurring in the H2A DNA-binding loops. In this study, we employ hydrogen-deuterium exchange coupled with mass spectrometry and molecular dynamics simulation to investigate the differences in solution behavior between human H2A-H2B and H2A.Z-H2B. We demonstrate that replacing H2A with H2A.Z enhances the dynamics of the histone dimer, whether it is free, complexed with H3-H4, or within the nucleosome. Enhanced dynamics are observed for H2B, suggesting altered interaction with H2A.Z and DNA. Parallel comparisons between H2A-H2B orthologs from humans and frogs show fewer differences in dynamics. Our findings provide mechanistic insights into the function of histone variants and reveal how differences in dynamics may underlie functional differences between structurally similar proteins.
HostingRepository	PRIDE
AnnounceDate	2025-12-30
AnnouncementXML	Submission_2025-12-29_19:10:58.972.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Sheena D'Arcy
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606; scientific name: Xenopus laevis (African clawed frog); NCBI TaxID: NEWT:8355;
ModificationList	monohydroxylated residue
Instrument	Synapt MS

Revision	Datetime	Status	ChangeLog Entry
0	2025-04-14 18:24:38	ID requested
⏵ 1	2025-12-29 19:10:59	announced

Dataset with its publication pending

submitter keyword: molecular dynamics,HDX-MS, chromatin regulation, histone variants

Sheena D'Arcy
contact affiliation	Chemistry Department, University of Texas at Dallas, Richardson. TX
contact email	sheena.darcy@utdallas.edu
lab head
Sheena D'Arcy
contact affiliation	The University of Texas at Dallas
contact email	sheena.darcy@utdallas.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD062956
     1. Label: PRIDE project
     2. Name: Histone variant H2A.Z enhances histone and nucleosome dynamics