PXD026638

PXD026638 is an original dataset announced via ProteomeXchange.

Title	Chromatin remodeler Brahma safeguards labile canalization of cardiac mesoderm differentiation
Description	Differentiation proceeds along a continuum of increasingly fate-restricted intermediates, referred to as canalization. Canalization is essential for stabilizing cell fate, but mechanisms underlying robust canalization are unclear. Here we show that the BRG1/BRM-associated factor (BAF) chromatin remodeling complex ATPase gene Brm safeguards cell identity during directed cardiogenesis of mouse embryonic stem cells. Despite establishment of well-differentiated precardiac mesoderm, Brm-null cells predominantly became neural precursors, violating germ layer assignment. Trajectory inference showed sudden acquisition of non-mesodermal identity in Brm-null cells, consistent with a new transition state referred to as a saddle-node bifurcation. Mechanistically, loss of Brm prevented de novo accessibility of cardiac enhancers while increasing expression of neurogenic factor POU3F1, preventing expression of neural suppressor REST, and disrupting composition of BRG1 complexes. Brm mutant identity switch was overcome by increasing BMP4 levels during mesoderm induction. Mathematical modeling supports all our observations. In the mouse embryo, Brm deletion exacerbated mesoderm-deleted Brg1 mutant phenotypes, severely compromising cardiogenesis, unmasking an in vivo role for Brm. Our results reveal Brm as a compensable safeguard of the fidelity of mesoderm chromatin states, and support a model in which developmental canalization is not a rigid irreversible path, but a highly plastic trajectory.
HostingRepository	PRIDE
AnnounceDate	2021-11-03
AnnouncementXML	Submission_2022-02-07_08:13:18.407.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Ruth Huttenhain
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2021-06-10 22:49:48	ID requested
1	2021-11-03 07:58:11	announced
⏵ 2	2022-02-07 08:13:19	announced	2022-02-07: Updated publication reference for PubMed record(s): 35082446.

Hota SK, Rao KS, Blair AP, Khalilimeybodi A, Hu KM, Thomas R, So K, Kameswaran V, Xu J, Polacco BJ, Desai RV, Chatterjee N, Hsu A, Muncie JM, Blotnick AM, Winchester SAB, Weinberger LS, H, ü, ttenhain R, Kathiriya IS, Krogan NJ, Saucerman JJ, Bruneau BG, Brahma safeguards canalization of cardiac mesoderm differentiation. Nature, 602(7895):129-134(2022) [pubmed]

submitter keyword: Cardiac differentiation, AP-MS

Ruth Huttenhain
contact affiliation	Celleluar and Molecular Pharmacology, UCSF
contact email	ruth.huttenhain@ucsf.edu
lab head
Ruth Huttenhain
contact affiliation	UCSF
contact email	ruth.huttenhain@ucsf.edu
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/2021/11/PXD026638

PRIDE project URI

• PRIDE
  1. PXD026638
     1. Label: PRIDE project
     2. Name: Chromatin remodeler Brahma safeguards labile canalization of cardiac mesoderm differentiation