PXD064106 is an
original dataset announced via ProteomeXchange.
Dataset Summary
| 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 |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|
| 0 | 2025-05-20 07:15:39 | ID requested | |
| ⏵ 1 | 2025-12-01 05:02:07 | announced | |
Publication List
Keyword List
| submitter keyword: Proximity biotinylation assay,Epigenetics, KRAB zinc finger proteins (KZFPs)., Cardiomyocytes, Transposable elements (TEs) |
Contact List
| 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 | |
Full Dataset Link List
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 |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD064106
- Label: PRIDE project
- Name: Tissue-specific restriction of TE-derived regulatory elements safeguards cell-type identity
