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Dev Cell. 2016 Mar 21;36(6):611-23. doi: 10.1016/j.devcel.2016.02.024.

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

Author information

1
School of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL), Station 19, 1015 Lausanne, Switzerland.
2
School of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL), Station 19, 1015 Lausanne, Switzerland. Electronic address: didier.trono@epfl.ch.

Abstract

KRAB-containing zinc finger proteins (KRAB-ZFPs) are early embryonic controllers of transposable elements (TEs), which they repress with their cofactor KAP1 through histone and DNA methylation, a process thought to result in irreversible silencing. Using a target-centered functional screen, we matched murine TEs with their cognate KRAB-ZFP. We found the paralogs ZFP932 and Gm15446 to bind overlapping but distinguishable subsets of ERVK (endogenous retrovirus K), repress these elements in embryonic stem cells, and regulate secondarily the expression of neighboring genes. Most importantly, we uncovered that these KRAB-ZFPs and KAP1 control TEs in adult tissues, in cell culture and in vivo, where they partner up to modulate cellular genes. Therefore, TEs and KRAB-ZFPs establish transcriptional networks that likely regulate not only development but also many physiological events. Given the high degree of species specificity of TEs and KRAB-ZFPs, these results have important implications for understanding the biology of higher vertebrates, including humans.

PMID:
27003935
PMCID:
PMC4896391
DOI:
10.1016/j.devcel.2016.02.024
[Indexed for MEDLINE]
Free PMC Article

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