title: Age-associated de-repression of retrotransposons in the Drosophila fat body, its potential cause and consequence.
abstract: Eukaryotic genomes contain transposable elements (TE) that can move into new locations upon activation. Since uncontrolled transposition of TEs, including the retrotransposons and DNA transposons, can lead to DNA breaks and genomic instability, multiple mechanisms, including heterochromatin-mediated repression, have evolved to repress TE activation. Studies in model organisms have shown that TEs become activated upon aging as a result of age-associated deregulation of heterochromatin. Considering that different organisms or cell types may undergo distinct heterochromatin changes upon aging, it is important to identify pathways that lead to TE activation in specific tissues and cell types. Through deep sequencing of isolated RNAs, we report an increased expression of many retrotransposons in the old Drosophila fat body, an organ equivalent to the mammalian liver and adipose tissue. This de-repression correlates with an increased number of DNA damage foci and decreased level of Drosophila lamin-B in the old fat body cells. Depletion of the Drosophila lamin-B in the young or larval fat body results in a reduction of heterochromatin and a corresponding increase in retrotransposon expression and DNA damage. Further manipulations of lamin-B and retrotransposon expression suggest a role of the nuclear lamina in maintaining the genome integrity of the Drosophila fat body by repressing retrotransposons.
authors.affiliation: Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, 510275, China.|Department of Embryology, Carnegie Institution for Science, Baltimore, MD, 21218, USA.
authors.forename: Haiyang
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Embryology, Carnegie Institution for Science, Baltimore, MD, 21218, USA.
authors.forename: Xiaobin
authors.initials: X
authors.lastname: Zheng
authors.affiliation: Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, 510275, China.
authors.forename: Danqing
authors.initials: D
authors.lastname: Xiao
authors.affiliation: Department of Embryology, Carnegie Institution for Science, Baltimore, MD, 21218, USA.
authors.forename: Yixian
authors.initials: Y
authors.lastname: Zheng
mesh_terms: D000375:Aging / Q000235:genetics*; D000818:Animals; D004249:DNA Damage / Q000235:genetics; D029721:Drosophila Proteins / Q000378:metabolism; D004331:Drosophila melanogaster / Q000235:genetics* / Q000254:growth & development*; D005216:Fat Body / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D006570:Heterochromatin / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D034882:Lamins / Q000378:metabolism; D008239:Lysine / Q000378:metabolism; D008745:Methylation; D008954:Models, Biological; D018626:Retroelements / Q000235:genetics*
chemical_list: D029721:Drosophila Proteins; D006570:Heterochromatin; D006657:Histones; C440328:Lam protein, Drosophila; D034882:Lamins; D018626:Retroelements; D008239:Lysine
keywords: DNA damage; Lamin-B; aging; heterochromatin; lamin Dm0; retrotransposons