PXD021616

PXD021616 is an original dataset announced via ProteomeXchange.

Title	MLL4-associated condensates counterbalance Polycomb-mediated nuclear mechanical stress in Kabuki Syndrome
Description	The genetic elements required to tune gene expression are partitioned in active and repressive nuclear condensates. Chromatin compartments include transcriptional clusters whose dynamic establishment and functioning depends on multivalent interactions occurring among transcription factors, cofactors and basal transcriptional machinery. However how chromatin players contribute to the assembly of transcriptional condensates has not been addressed. By interrogating the effect of KMT2D haploinsufficiency in Kabuki Syndrome, we found that MLL4 contributes in the assembly of transcriptional condensates through liquid-liquid phase separation. MLL4 loss-of-function impaired Polycomb-dependent chromatin compartmentalization, altering nuclear architecture. By releasing the nuclear mechanical stress through the inhibition of the mechano-sensor ATR, we re-established the mechano-signaling of mesenchymal stem cells and their commitment towards chondrocytes both in vitro and in vivo. This study supports the notion that in Kabuki Syndrome the haploinsufficiency of MLL4 causes an altered functional partitioning of chromatin, which determines the architecture and mechanical properties of the nucleus.
HostingRepository	PRIDE
AnnounceDate	2020-09-22
AnnouncementXML	Submission_2020-09-22_04:56:06.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Romina Belli
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monomethylated residue; trimethylated residue; acetylated residue; dimethylated residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2020-09-22 04:34:58	ID requested
⏵ 1	2020-09-22 04:56:06	announced

Dataset with its publication pending

submitter keyword: Mass spectrometry, PTM, Epiprofile, Histone, Kabuki Syndrome

Zippo Alessio
contact affiliation	Laboratory of Chromatin Biology & Epigenetics, Department of Cellular, Computational and Integrative Biology (CIBIO), University of Trento, 38123 Trento, Italy
contact email	alessio.zippo@unitn.it
lab head
Romina Belli
contact affiliation	University of Trento
contact email	romina.belli@unitn.it
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/2020/09/PXD021616

PRIDE project URI

• PRIDE
  1. PXD021616
     1. Label: PRIDE project
     2. Name: MLL4-associated condensates counterbalance Polycomb-mediated nuclear mechanical stress in Kabuki Syndrome