Transposable Elements and Their KRAB-ZFP Controllers Regulate Gene Expression in Adult Tissues
| Autor: | Marco Cassano, Annamaria Kauzlaric, Helen M. Rowe, Priscilla Turelli, Andrea Coluccio, Didier Trono, Michael Imbeault, Gabriela Ecco, Julien Duc, Sandra Offner |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Cellular differentiation Molecular Sequence Data Endogenous retrovirus Retrotransposon Tripartite Motif-Containing Protein 28 Article General Biochemistry Genetics and Molecular Biology Mice 03 medical and health sciences 0302 clinical medicine Animals Humans Gene silencing Amino Acid Sequence Molecular Biology Embryonic Stem Cells Mice Knockout Zinc finger Regulation of gene expression Genetics biology Endogenous Retroviruses Nuclear Proteins food and beverages Cell Differentiation Zinc Fingers Cell Biology Repressor Proteins 030104 developmental biology Histone Gene Expression Regulation DNA methylation DNA Transposable Elements biology.protein 030217 neurology & neurosurgery Developmental Biology |
| Zdroj: | Developmental Cell |
| ISSN: | 1534-5807 |
| Popis: | 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), to repress these elements in embryonic stem cells, and to 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 regulate not only development but probably 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. |
| Databáze: | OpenAIRE |
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