PXD003145

PXD003145 is an original dataset announced via ProteomeXchange.

Title	Elf5-centered transcription factor hub controls trophoblast stem cell self-renewal and differentiation through stoichiometry-sensitive shifts in target gene networks
Description	Elf5 is a transcription factor with pivotal roles in the trophoblast compartment where it reinforces a trophoblast stem cell (TSC)-specific transcriptional circuit. However, Elf5 is also present in differentiating trophoblast cells that have ceased to express other TSC genes such as Cdx2 and Eomes. In the current study we aimed to elucidate the context-dependent role of Elf5 at the interface between TSC self-renewal and onset of differentiation. We demonstrate that precise levels of Elf5 are critical for normal expansion of the TSC compartment and embryonic survival, as Elf5 overexpression triggers precocious trophoblast differentiation. Through integration of protein interactome, transcriptome and genome-wide chromatin immunoprecipitation data we reveal that this abundance-dependent function is mediated through a shift in preferred Elf5 binding partners; in TSCs, Elf5 interaction with Eomes recruits Tfap2c to triply occupied sites at TSC-specific genes driving their expression. By contrast, the Elf5 and Tfap2c interaction becomes predominant as their protein levels increase. This triggers binding to double and single occupancy sites that harbour the cognate Tfap2c motif, causing activation of the associated differentiation-promoting genes. These data place Elf5 at the centre of a stoichiometry-sensitive transcriptional network where it acts as molecular switch governing the balance between TSC proliferation and differentiation.
HostingRepository	PRIDE
AnnounceDate	2015-12-01
AnnouncementXML	Submission_2015-12-01_10:05:34.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	David Oxley
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	monohydroxylated residue
Instrument	LTQ Orbitrap Velos

Revision	Datetime	Status	ChangeLog Entry
0	2015-11-04 03:05:22	ID requested
⏵ 1	2015-12-01 10:05:35	announced

Dataset with its publication pending

curator keyword: Biological

submitter keyword: Elf5, Trophoblast Stem Cells, Differentiation, LC-MSMS

david oxley
contact affiliation	Babraham Institute Cambridge UK
contact email	david.oxley@babraham.ac.uk
lab head
David Oxley
contact affiliation	Babraham Institute
contact email	david.oxley@babraham.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD003145
     1. Label: PRIDE project
     2. Name: Elf5-centered transcription factor hub controls trophoblast stem cell self-renewal and differentiation through stoichiometry-sensitive shifts in target gene networks