PXD057198

PXD057198 is an original dataset announced via ProteomeXchange.

Title	Sirtuin 7 regulates Xa-hyperactivation to balance the X-chromosome against the genome
Description	Sirtuins are deacetylases implicated in stress responses and longevity in mammals. Although their differential impact on the two sexes has been noted, underlying causes for sex biases in aging and cancer are not known. Here, using Sirtuin 7 (SIRT7) as a model in mice, we probe mechanisms leading to sex differences. We find that Sirt7-/- females have decreased fitness during embryogenesis and throughout life. Intriguingly, SIRT7 preferentially localizes to the X-chromosome, suggesting a potential defect in X-inactivation — the arm of dosage compensation that equalizes X-chromosome expression between XX females and XY males. Indeed, SIRT7 ablation causes increased Xist RNA levels, H3K27me3 enrichment, and gene repression on the inactive X (Xi) chromosome. Surprisingly, however, loss of SIRT7 exerts greatest effects on the active X (Xa). In Sirt7-/- females, the Xa demonstrates 3D structural disorganization, increased chromatin mixing, and acute propensity to break and form chromosome fusions in an Xa-specific manner. Disproportional to autosomes and Xi, the Xa becomes super-acetylated on H3K36 and super-activated in gene expression, resulting in an imbalance in the 2nd arm of dosage compensation — known as “Xa-hyperactivation” — which evolved to balance X-linked gene expression against the genome. These data reveal a crosstalk between sirtuins and dosage compensation and identify a novel regulator of Xa-hyperactivation.
HostingRepository	PRIDE
AnnounceDate	2026-03-27
AnnouncementXML	Submission_2026-03-27_07:56:06.456.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Joan Josep Bech-Serra
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	phosphorylated residue; acetylated residue
Instrument	Orbitrap Eclipse

Revision	Datetime	Status	ChangeLog Entry
0	2024-10-25 07:39:43	ID requested
⏵ 1	2026-03-27 07:56:06	announced

Dataset with its publication pending

submitter keyword: SIRT7, Label Free, acetylation, X-chromosome, phosphorylation, MaxQuant, EZH2,Sirtuin 7

Nicolas Simonet
contact affiliation	Department of Molecular Biology, Massachusetts General Hospital, Boston, MA, USA; Department of Genetics, The Blavatnik Institute, Harvard Medical School, Boston, MA, USA.
contact email	nsimonet@molbio.mgh.harvard.edu
lab head
Joan Josep Bech-Serra
contact affiliation	Proteomics Unit - Josep Carreras Leukaemia Research Institute
contact email	jbech@carrerasresearch.org
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD057198
     1. Label: PRIDE project
     2. Name: Sirtuin 7 regulates Xa-hyperactivation to balance the X-chromosome against the genome