Transposable Elements and Their KRAB-ZFP Controllers Regulate Gene Expression in Adult Tissues

Area of Science:

• Genetics
• Molecular Biology
• Epigenetics

Background:

• Transposable elements (TEs) are mobile genetic sequences that can impact genome stability and gene regulation.
• KRAB-containing zinc finger proteins (KRAB-ZFPs) are known regulators of TEs, primarily studied in early embryonic development.
• The silencing mechanism mediated by KRAB-ZFPs and KAP1 was presumed to be irreversible.

Purpose of the Study:

• To identify specific KRAB-ZFPs that target murine transposable elements (TEs).
• To investigate the role of KRAB-ZFPs and KAP1 in regulating TEs beyond early embryonic stages.
• To understand the broader implications of TE-KRAB-ZFP interactions in transcriptional networks.

Main Methods:

• A target-centered functional screen was employed to match murine TEs with their cognate KRAB-ZFPs.
• Functional assays were conducted in embryonic stem cells, adult tissues, cell culture, and in vivo models.
• Gene expression analysis and epigenetic modification studies were performed.

Main Results:

• Paralogs ZFP932 and Gm15446 were identified to bind distinct subsets of ERVK (endogenous retrovirus K) elements.
• These KRAB-ZFPs, along with KAP1, repress ERVK elements in embryonic stem cells and regulate neighboring gene expression.
• KRAB-ZFPs and KAP1 were found to control TEs and modulate cellular genes in adult tissues, cell culture, and in vivo.

Conclusions:

• KRAB-ZFPs and KAP1 actively control transposable elements in both embryonic and adult stages.
• TEs and KRAB-ZFPs form transcriptional networks with implications for development and physiological events.
• The species-specific nature of TEs and KRAB-ZFPs highlights their importance in higher vertebrate and human biology.