PXD046457-2

PXD046457 is an original dataset announced via ProteomeXchange.

Title	A SIRT7-dependent acetylation switch regulates early B-cell differentiation and lineage commitment through PAX5
Description	B lymphopoiesis is a key developmental event orchestrated by a complex combinatorial action of lineage-specific transcription factors. In early B cell progenitors, lineage commitment is directly mediated by the master regulator PAX5, whose deficiency is commonly associated with B cell Acute Lymphoblastic Leukemia (B-ALL). Despite its essential role in mammalian immunity, the regulatory mechanisms that control PAX5 function remain largely unknown. Here we show that NAD+-dependent enzyme SIRT7 coordinates B cell development progression through PAX5. We have identified a SIRT7-dependent regulatory switch based on dynamic deacetylation of a single PAX5 residue, which controls its activity and thereby B cell fate. While a PAX5K198 acetylated mimic is incapable of inducing both B cell development and identity due to reduced protein stability and impaired binding to chromatin, deacetylation of this residue boosts PAX5 activity, leading to massive gene repression and in vivo restoration of B cell commitment but not differentiation. These findings suggest an unexpected uncoupling of hematopoietic differentiation and lineage commitment. Further supporting the functional relevance of the SIRT7-PAX5 axis, the interplay between both factors is conserved in human B-ALL, where high SIRT7 expression is an independent good prognostic factor. Our findings unveil a crucial mechanism in the regulation of B cell production based on the control of PAX5 function and underscore the key role of Sirtuins in the regulation of the immune system.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:59:11.910.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: 10090;
ModificationList	acetylated residue
Instrument	orbitrap

Revision	Datetime	Status	ChangeLog Entry
0	2023-10-27 07:31:44	ID requested
1	2024-09-20 00:11:09	announced
⏵ 2	2024-10-22 06:59:12	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

submitter keyword: Sirtuins, SIRT7, acetylation, PAX5, B cell progenitors, Pre-B cell, hematopoiesis, immunoaffinity

Alex Vaquero
contact affiliation	Chromatin Biology Laboratory, Josep Carreras Leukaemia Research Institute (IJC), Ctra de Can Ruti, Camí de les Escoles s/n, 08916, Badalona, Barcelona, Spain
contact email	avaquero@carrerasresearch.org
lab head
Joan Josep Bech-Serra
contact affiliation	Proteomics Unit - Josep Carreras Leukaemia Research Institute
contact email	jbech@carrerasresearch.org
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/2024/09/PXD046457

PRIDE project URI

• PRIDE
  1. PXD046457
     1. Label: PRIDE project
     2. Name: A SIRT7-dependent acetylation switch regulates early B-cell differentiation and lineage commitment through PAX5