SIRT6 represses LINE1 retrotransposons by ribosylating KAP1 but this repression fails with stress and age
| Autor: | Michael Van Meter, Anthony J. Geneva, Sarallah Rezazadeh, Timothy D. Morello, Vera Gorbunova, Mehr Kashyap, Andrei Seluanov |
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| Rok vydání: | 2014 |
| Předmět: |
Aging
Chromatin Immunoprecipitation Heterochromatin General Physics and Astronomy Repressor Retrotransposon Biology Tripartite Motif-Containing Protein 28 Real-Time Polymerase Chain Reaction Genome General Biochemistry Genetics and Molecular Biology Article Mice Stress Physiological Animals Immunoprecipitation Sirtuins Sulfites Nuclear protein Luciferases DNA Primers Genetics Mice Knockout Multidisciplinary Nuclear Proteins General Chemistry Repressor Proteins Long Interspersed Nucleotide Elements Histone deacetylase Corepressor Chromatin immunoprecipitation |
| Zdroj: | Nature communications |
| ISSN: | 2041-1723 |
| Popis: | L1 retrotransposons are an abundant class of transposable elements that pose a threat to genome stability and may have a role in age-related pathologies such as cancer. Recent evidence indicates that L1s become more active in somatic tissues during the course of ageing; however the mechanisms underlying this phenomenon remain unknown. Here we report that the longevity regulating protein, SIRT6, is a powerful repressor of L1 activity. Specifically, SIRT6 binds to the 5′-UTR of L1 loci, where it mono-ADP ribosylates the nuclear corepressor protein, KAP1, and facilitates KAP1 interaction with the heterochromatin factor, HP1α, thereby contributing to the packaging of L1 elements into transcriptionally repressive heterochromatin. During the course of ageing, and also in response to DNA damage, however, we find that SIRT6 is depleted from L1 loci, allowing the activation of these previously silenced retroelements. Retrotransposons are repetitive sequences in the genome that can amplify themselves and whose activity has been linked to age-related pathologies. Here, Van Meter et al.report that the histone deacetylase SIRT6 represses activity of the L1 retrotransposon by ribosylating the nuclear corepressor protein, KAP1. |
| Databáze: | OpenAIRE |
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