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PXD026638 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleChromatin remodeler Brahma safeguards labile canalization of cardiac mesoderm differentiation
DescriptionDifferentiation 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.
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterRuth Huttenhain
SpeciesList scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationListmonohydroxylated residue; iodoacetamide derivatized residue
InstrumentOrbitrap Fusion Lumos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02021-06-10 22:49:48ID requested
12021-11-03 07:58:11announced
22022-02-07 08:13:19announced2022-02-07: Updated publication reference for PubMed record(s): 35082446.
Publication List
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, ΓΌ, ttenhain R, Kathiriya IS, Krogan NJ, Saucerman JJ, Bruneau BG, Brahma safeguards canalization of cardiac mesoderm differentiation. Nature, 602(7895):129-134(2022) [pubmed]
Keyword List
submitter keyword: Cardiac differentiation, AP-MS
Contact List
Ruth Huttenhain
contact affiliationCelleluar and Molecular Pharmacology, UCSF
contact emailruth.huttenhain@ucsf.edu
lab head
Ruth Huttenhain
contact affiliationUCSF
contact emailruth.huttenhain@ucsf.edu
dataset submitter
Full Dataset Link List
Dataset FTP location
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