PXD031059-1

PXD031059 is an original dataset announced via ProteomeXchange.

Title	The multi-lineage transcription factor ISL1 controls cardiomyocyte cell fate through interaction with NKX2.5
Description	Congenital heart disease (CHD) is a leading cause of infant mortality in the US and is commonly thought to arise from perturbations of transcription factors (TFs) during cardiac development. ISLET1 (ISL1) is one such TF, although it also directs differentiation of other cell types, including motor neuron progenitors (MNPs) and pancreatic islet cells. Although cellular specificity of ISL1 function is likely achieved through combinatorial interactions, its essential cardiac interacting partners are unknown. By assaying ISL1 genomic occupancy in human iPSC-derived cardiac progenitors (CPs) or MNPs and leveraging the deep learning approach BPNet, we identified cell-type-specific motifs of other TFs that predicted ISL1 occupancy in each lineage, with the NKX2.5 motif being most closely associated to ISL1 in CPs. We demonstrated ISL1 forms a protein complex with NKX2.5 in CPs, and the two regulated similar gene networks. NKX2.5 co-occupied more than half of ISL1-bound loci, and ISL1 was dependent on NKX2.5 for CP-specific localization. Furthermore, overexpression of NKX2.5 in MNPs led to ISL1 redistribution to CP-specific loci. These results reveal how ISL1 can guide differential lineage choices through a combinatorial code that dictates genomic occupancy and transcription.
HostingRepository	PanoramaPublic
AnnounceDate	2023-10-17
AnnouncementXML	Submission_2023-10-17_20:05:25.097.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	supported by repository but incomplete data and/or metadata
PrimarySubmitter	Ruth Huttenhain
SpeciesList	scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationList	Carbamidomethyl; Label:13C(6)15N(2); Label:13C(6)15N(4)
Instrument	TSQ Quantiva

Revision	Datetime	Status	ChangeLog Entry
0	2022-01-18 11:11:09	ID requested
⏵ 1	2023-10-17 20:05:25	announced

Maven et al., The multi-lineage transcription factor ISL1 controls cardiomyocyte cell fate through interaction with NKX2.5, Stem Cell Reports (2023), https://doi.org/10.1016/j.stemcr.2023.09.014

submitter keyword: SRM, cardiomyocytes, transcription factors

Ruth Huttenhain
contact affiliation	Department of Cellular and Molecular Pharmacology, UCSF
contact email	ruth.huttenhain@ucsf.edu
lab head
Ruth Huttenhain
contact affiliation	Department of Cellular and Molecular Pharmacology, UCSF
contact email	ruth.huttenhain@ucsf.edu
dataset submitter

Panorama Public dataset URI