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research article

Evolutionally dynamic L1 regulation in embryonic stem cells

Castro-Diaz, Nathaly
•
Ecco, Gabriela  
•
Coluccio, Andrea  
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2014
Genes & Development

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 [Krüppel-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.

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Type
research article
DOI
10.1101/gad.241661.114
Web of Science ID

WOS:000338816000003

Author(s)
Castro-Diaz, Nathaly
Ecco, Gabriela  
Coluccio, Andrea  
Kapopoulou, Adamandia  
Yazdanpanah, Benyamin
Friedli, Marc
Duc, Julien
Jang, Suk Min  
Turelli, Priscilla  
Trono, Didier  
Date Issued

2014

Publisher

Cold Spring Harbor Lab Press, Publications Dept

Published in
Genes & Development
Volume

28

Issue

13

Start page

1397

End page

409

Subjects

Gene Expression Regulation

Editorial or Peer reviewed

NON-REVIEWED

Written at

EPFL

EPFL units
LVG  
Available on Infoscience
June 19, 2014
Use this identifier to reference this record
https://infoscience.epfl.ch/handle/20.500.14299/104538
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