PXD064106

PXD064106 is an original dataset announced via ProteomeXchange.

Title	Tissue-specific restriction of TE-derived regulatory elements safeguards cell-type identity
Description	Transposable elements (TEs) have extensively reshaped the cis-regulatory landscape of mammalian genomes, yet the mechanisms that govern their context-specific activity remain incompletely understood. KRAB zinc finger proteins (KZFPs), a large family of transcription factors specialized in TE recognition, are known repressors of TE-derived regulatory activity through TRIM28-mediated H3K9me3 deposition. Here, we expand this paradigm by uncovering noncanonical relationships between TEs and KZFPs. By generating a comprehensive epigenomic map of KZFP-bound TEs, we find that the regulatory activity of ancient mammalian L2/MIR elements is broadly delineated by KZFP binding patterns, despite low H3K9me3 enrichment. We further dissect this relationship by investigating the function of ZNF436, a non-canonical KZFP, highly expressed during in vivo human fetal heart development. Using loss-of-function approaches, we show that ZNF436 preserves cardiomyocyte function by promoting cardiac gene expression while restricting the activation of alternative lineage programs. Mechanistically, ZNF436 recruits specialized SWI/SNF chromatin remodeling complexes to limit the accessibility of L2/MIR-derived enhancers, many of which are active in non-cardiac tissues. These findings reveal a noncanonical, TRIM28-independent role for KZFPs in shaping cell-type-specific regulatory landscapes and emphasize the importance of repressing alternative regulatory programs alongside activating lineage-specific ones to safeguard cell identity.
HostingRepository	PRIDE
AnnounceDate	2025-12-01
AnnouncementXML	Submission_2025-12-01_05:02:07.222.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Romain Hamelin
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2025-05-20 07:15:39	ID requested
⏵ 1	2025-12-01 05:02:07	announced

10.1101/2025.05.13.6537;

submitter keyword: Proximity biotinylation assay,Epigenetics, KRAB zinc finger proteins (KZFPs)., Cardiomyocytes, Transposable elements (TEs)

Didier Trono
contact affiliation	School of Life Science, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland
contact email	didier.trono@epfl.ch
lab head
Romain Hamelin
contact affiliation	PCF
contact email	romain.hamelin@epfl.ch
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/2025/12/PXD064106

PRIDE project URI

• PRIDE
  1. PXD064106
     1. Label: PRIDE project
     2. Name: Tissue-specific restriction of TE-derived regulatory elements safeguards cell-type identity