Publication

Tissue-specific restriction of transposon-derived regulatory elements safeguards cell-type identity

2026

Abstract

Transposable elements (TEs) reshape mammalian cis-regulatory landscapes, but the mechanisms controlling their context-specific activity remain unclear. KRAB zinc finger proteins (KZFPs) typically repress TE-derived regulatory activity via TRIM28-mediated H3K9me3 deposition. We expand this paradigm by uncovering non-canonical KZFP-TE relationships. Through comprehensive epigenomic mapping of KZFP-bound TEs, we show that ancient mammalian L2/MIR elements' regulatory activity is delineated by KZFP binding despite low H3K9me3 enrichment. We dissect this relationship by focusing on ZNF436, a non-canonical KZFP highly expressed in the developing human heart. We find that ZNF436 preserves cardiomyocyte function by promoting cardiac gene expression while restricting alternative lineage programs. Mechanistically, ZNF436 associates with the SWI/SNF remodeling complex to limit the accessibility of L2/MIR-derived CREs, otherwise active in non-cardiac tissues. Our findings reveal a TRIM28-independent role for KZFPs in shaping cell-type-specific regulatory landscapes and emphasize the importance of repressing alternative lineage programs while activating lineage-specific ones to safeguard cell identity.

Official source

https://infoscience.epfl.ch/entities/publication/aaa5f7e1-8a51-4166-a2ba-f06065f74649

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2026

Abstract

Official source

https://infoscience.epfl.ch/entities/publication/aaa5f7e1-8a51-4166-a2ba-f06065f74649

About this result

Related concepts (32)

Cardiac arrest

Cardiac arrest occurs when the heart stops beating. It is defined as cessation of normal circulation of blood due to failure of the heart to pump effectively. It is a medical emergency that, without immediate medical intervention, will result in cardiac death within minutes. When it happens suddenly, it is called sudden cardiac arrest. Cardiopulmonary resuscitation (CPR) and possibly defibrillation are needed until further treatment can be provided. Cardiac arrest results in a rapid loss of consciousness, and breathing may be abnormal or absent.

Transposable element

A transposable element (TE, transposon, or jumping gene) is a nucleic acid sequence in DNA that can change its position within a genome, sometimes creating or reversing mutations and altering the cell's genetic identity and genome size. Transposition often results in duplication of the same genetic material. In the human genome, L1 and Alu elements are two examples. Barbara McClintock's discovery of them earned her a Nobel Prize in 1983.

Epigenetics

In biology, epigenetics is the study of stable changes in cell function (known as marks) that do not involve alterations in the DNA sequence. The Greek prefix epi- (ἐπι- "over, outside of, around") in epigenetics implies features that are "on top of" or "in addition to" the traditional genetic basis for inheritance. Epigenetics most often involves changes that affect the regulation of gene expression, and that persist through cellular division.