PXD054928-1

PXD054928 is an original dataset announced via ProteomeXchange.

Title	Control of cell identity and early neural fate commitment by the enhancer module of Integrator
Description	Lineage-specific transcription factors (TFs) operate as master orchestrators of developmental processes by activating select cis-regulatory enhancers and proximal promoters. Direct DNA binding of TFs ultimately drives context-specific recruitment of the basal transcriptional machinery that comprises RNA Polymerase II (RNAPII) and a host of polymerase-associated multiprotein complexes, including the metazoan-specific Integrator complex. Integrator is primarily known to modulate RNAPII processivity and to surveil RNA integrity across coding genes. Here we show an enhancer module of Integrator that directs cell fate specification by promoting epigenetic changes and TF binding at neural enhancers. Depletion of Integrator’s INTS10 upends neural traits and derails cells towards mesenchymal identity. Commissioning of neural enhancers relies on Integrator’s enhancer module, which stabilizes SOX2 binding at chromatin upon exit from pluripotency. We propose Integrator as a functional bridge between enhancers and promoters and a main driver of early development, providing new insight into a growing family of neurodevelopmental syndromes.
HostingRepository	PRIDE
AnnounceDate	2024-08-15
AnnouncementXML	Submission_2024-08-15_06:47:38.425.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Kelsey Leach
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2024-08-15 02:57:52	ID requested
⏵ 1	2024-08-15 06:47:38	announced
2	2024-10-22 06:55:17	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

submitter keyword: iPSCs, human,Integrator, transcription factors

Alessandro Gardini
contact affiliation	The Wistar Institute, 3601 Spruce St, Philadelphia, PA 19103, USA
contact email	agardini@wistar.org
lab head
Kelsey Leach
contact affiliation	The Wistar Institute
contact email	kleach@wistar.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/2024/08/PXD054928

PRIDE project URI

• PRIDE
  1. PXD054928
     1. Label: PRIDE project
     2. Name: Control of cell identity and early neural fate commitment by the enhancer module of Integrator