title: Transposable Elements and Their KRAB-ZFP Controllers Regulate Gene Expression in Adult Tissues.
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.
authors.affiliation: School of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL), Station 19, 1015 Lausanne, Switzerland.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Ecco
authors.affiliation: School of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL), Station 19, 1015 Lausanne, Switzerland.
authors.forename: Marco
authors.initials: M
authors.lastname: Cassano
authors.affiliation: School of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL), Station 19, 1015 Lausanne, Switzerland.
authors.forename: Annamaria
authors.initials: A
authors.lastname: Kauzlaric
authors.affiliation: School of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL), Station 19, 1015 Lausanne, Switzerland.
authors.forename: Julien
authors.initials: J
authors.lastname: Duc
authors.affiliation: School of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL), Station 19, 1015 Lausanne, Switzerland.
authors.forename: Andrea
authors.initials: A
authors.lastname: Coluccio
authors.affiliation: School of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL), Station 19, 1015 Lausanne, Switzerland.
authors.forename: Sandra
authors.initials: S
authors.lastname: Offner
authors.affiliation: School of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL), Station 19, 1015 Lausanne, Switzerland.
authors.forename: Michaël
authors.initials: M
authors.lastname: Imbeault
authors.affiliation: School of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL), Station 19, 1015 Lausanne, Switzerland.
authors.forename: Helen M
authors.initials: HM
authors.lastname: Rowe
authors.affiliation: School of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL), Station 19, 1015 Lausanne, Switzerland.
authors.forename: Priscilla
authors.initials: P
authors.lastname: Turelli
authors.affiliation: School of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL), Station 19, 1015 Lausanne, Switzerland. Electronic address: didier.trono@epfl.ch.
authors.forename: Didier
authors.initials: D
authors.lastname: Trono
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002454:Cell Differentiation; D004251:DNA Transposable Elements / Q000235:genetics*; D053595:Embryonic Stem Cells / Q000378:metabolism; D020077:Endogenous Retroviruses / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism*; D000076183:Tripartite Motif-Containing Protein 28; D016335:Zinc Fingers / Q000235:genetics*
chemical_list: D004251:DNA Transposable Elements; D009687:Nuclear Proteins; D012097:Repressor Proteins; C103190:Trim28 protein, mouse; D000076183:Tripartite Motif-Containing Protein 28