RT Journal Article
T1 LINE-1 Evasion of Epigenetic Repression in Humans.
A1 Sanchez-Luque, Francisco J
A1 Kempen, Marie-Jeanne H C
A1 Gerdes, Patricia
A1 Vargas-Landin, Dulce B
A1 Richardson, Sandra R
A1 Troskie, Robin-Lee
A1 Jesuadian, J Samuel
A1 Cheetham, Seth W
A1 Carreira, Patricia E
A1 Salvador-Palomeque, Carmen
A1 García-Cañadas, Marta
A1 Muñoz-Lopez, Martin
A1 Sanchez, Laura
A1 Lundberg, Mischa
A1 Macia, Angela
A1 Heras, Sara R
A1 Brennan, Paul M
A1 Lister, Ryan
A1 Garcia-Perez, Jose L
A1 Ewing, Adam D
A1 Faulkner, Geoffrey J
K1 DNA methylation
K1 L1
K1 LINE-1
K1 YY1
K1 epigenetics
K1 neuroscience
K1 retrotransposon
K1 single-cell genomics
AB Epigenetic silencing defends against LINE-1 (L1) retrotransposition in mammalian cells. However, the mechanisms that repress young L1 families and how L1 escapes to cause somatic genome mosaicism in the brain remain unclear. Here we report that a conserved Yin Yang 1 (YY1) transcription factor binding site mediates L1 promoter DNA methylation in pluripotent and differentiated cells. By analyzing 24 hippocampal neurons with three distinct single-cell genomic approaches, we characterized and validated a somatic L1 insertion bearing a 3' transduction. The source (donor) L1 for this insertion was slightly 5' truncated, lacked the YY1 binding site, and was highly mobile when tested in vitro. Locus-specific bisulfite sequencing revealed that the donor L1 and other young L1s with mutated YY1 binding sites were hypomethylated in embryonic stem cells, during neurodifferentiation, and in liver and brain tissue. These results explain how L1 can evade repression and retrotranspose in the human body.
YR 2019
FD 2019-06-20
LK http://hdl.handle.net/10668/14159
UL http://hdl.handle.net/10668/14159
LA en
DS RISalud
RD Apr 6, 2025