PMID- 24939876 OWN - NLM STAT- MEDLINE DCOM- 20140902 LR - 20220311 IS - 1549-5477 (Electronic) IS - 0890-9369 (Print) IS - 0890-9369 (Linking) VI - 28 IP - 13 DP - 2014 Jul 1 TI - Evolutionally dynamic L1 regulation in embryonic stem cells. PG - 1397-409 LID - 10.1101/gad.241661.114 [doi] AB - Mobile elements are important evolutionary forces that challenge genomic integrity. Long interspersed element-1 (L1, also known as LINE-1) is the only autonomous transposon still active in the human genome. It displays an unusual pattern of evolution, with, at any given time, a single active L1 lineage amplifying to thousands of copies before getting replaced by a new lineage, likely under pressure of host restriction factors, which act notably by silencing L1 expression during early embryogenesis. Here, we demonstrate that in human embryonic stem (hES) cells, KAP1 (KRAB [Kruppel-associated box domain]-associated protein 1), the master cofactor of KRAB-containing zinc finger proteins (KRAB-ZFPs) previously implicated in the restriction of endogenous retroviruses, represses a discrete subset of L1 lineages predicted to have entered the ancestral genome between 26.8 million and 7.6 million years ago. In mice, we documented a similar chronologically conditioned pattern, albeit with a much contracted time scale. We could further identify an L1-binding KRAB-ZFP, suggesting that this rapidly evolving protein family is more globally responsible for L1 recognition. KAP1 knockdown in hES cells induced the expression of KAP1-bound L1 elements, but their younger, human-specific counterparts (L1Hs) were unaffected. Instead, they were stimulated by depleting DNA methyltransferases, consistent with recent evidence demonstrating that the PIWI-piRNA (PIWI-interacting RNA) pathway regulates L1Hs in hES cells. Altogether, these data indicate that the early embryonic control of L1 is an evolutionarily dynamic process and support a model in which newly emerged lineages are first suppressed by DNA methylation-inducing small RNA-based mechanisms before KAP1-recruiting protein repressors are selected. CI - (c) 2014 Castro-Diaz et al.; Published by Cold Spring Harbor Laboratory Press. FAU - Castro-Diaz, Nathaly AU - Castro-Diaz N AD - School of Life Sciences, Ecole Polytechnique Federale de Lausanne (EPFL), 1015 Lausanne, Switzerland. FAU - Ecco, Gabriela AU - Ecco G AD - School of Life Sciences, Ecole Polytechnique Federale de Lausanne (EPFL), 1015 Lausanne, Switzerland. FAU - Coluccio, Andrea AU - Coluccio A AD - School of Life Sciences, Ecole Polytechnique Federale de Lausanne (EPFL), 1015 Lausanne, Switzerland. FAU - Kapopoulou, Adamandia AU - Kapopoulou A AD - School of Life Sciences, Ecole Polytechnique Federale de Lausanne (EPFL), 1015 Lausanne, Switzerland. FAU - Yazdanpanah, Benyamin AU - Yazdanpanah B AD - School of Life Sciences, Ecole Polytechnique Federale de Lausanne (EPFL), 1015 Lausanne, Switzerland. FAU - Friedli, Marc AU - Friedli M AD - School of Life Sciences, Ecole Polytechnique Federale de Lausanne (EPFL), 1015 Lausanne, Switzerland. FAU - Duc, Julien AU - Duc J AD - School of Life Sciences, Ecole Polytechnique Federale de Lausanne (EPFL), 1015 Lausanne, Switzerland. FAU - Jang, Suk Min AU - Jang SM AD - School of Life Sciences, Ecole Polytechnique Federale de Lausanne (EPFL), 1015 Lausanne, Switzerland. FAU - Turelli, Priscilla AU - Turelli P AD - School of Life Sciences, Ecole Polytechnique Federale de Lausanne (EPFL), 1015 Lausanne, Switzerland. FAU - Trono, Didier AU - Trono D AD - School of Life Sciences, Ecole Polytechnique Federale de Lausanne (EPFL), 1015 Lausanne, Switzerland. LA - eng SI - GEO/GSE57989 SI - GEO/GSE58323 GR - 268721/ERC_/European Research Council/International PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140617 PL - United States TA - Genes Dev JT - Genes & development JID - 8711660 RN - 0 (Repressor Proteins) RN - EC 2.1.1.37 (DNA (Cytosine-5-)-Methyltransferases) RN - EC 2.3.2.27 (TRIM28 protein, human) RN - EC 2.3.2.27 (Tripartite Motif-Containing Protein 28) SB - IM CIN - Genes Dev. 2014 Jul 1;28(13):1381-3. PMID: 24990961 MH - Animals MH - DNA (Cytosine-5-)-Methyltransferases/metabolism MH - DNA Methylation MH - Embryonic Stem Cells MH - Evolution, Molecular MH - *Gene Expression Regulation MH - Humans MH - Long Interspersed Nucleotide Elements/*genetics MH - Mice MH - Repressor Proteins/genetics MH - Tripartite Motif-Containing Protein 28 PMC - PMC4083085 OTO - NOTNLM OT - DNA methylation OT - KAP1 OT - KRAB-ZFPs OT - LINE1 OT - embryonic stem cells OT - evolution EDAT- 2014/06/19 06:00 MHDA- 2014/09/03 06:00 PMCR- 2015/01/01 CRDT- 2014/06/19 06:00 PHST- 2014/06/19 06:00 [entrez] PHST- 2014/06/19 06:00 [pubmed] PHST- 2014/09/03 06:00 [medline] PHST- 2015/01/01 00:00 [pmc-release] AID - gad.241661.114 [pii] AID - 10.1101/gad.241661.114 [doi] PST - ppublish SO - Genes Dev. 2014 Jul 1;28(13):1397-409. doi: 10.1101/gad.241661.114. Epub 2014 Jun 17.