RRC ID 21884
著者 Vujatovic O, Zaragoza K, Vaquero A, Reina O, Bernués J, Azorín F.
タイトル Drosophila melanogaster linker histone dH1 is required for transposon silencing and to preserve genome integrity.
ジャーナル Nucleic Acids Res
Abstract Histone H1 is an intrinsic component of chromatin, whose important contribution to chromatin structure is well-established in vitro. Little is known, however, about its functional roles in vivo. Here, we have addressed this question in Drosophila, a model system offering many advantages since it contains a single dH1 variant. For this purpose, RNAi was used to efficiently deplete dH1 in flies. Expression-profiling shows that dH1 depletion affects expression of a relatively small number of genes in a regional manner. Furthermore, depletion up-regulates inactive genes, preferentially those located in heterochromatin, while active euchromatic genes are down-regulated, suggesting that the contribution of dH1 to transcription regulation is mainly structural, organizing chromatin for proper gene-expression regulation. Up-regulated genes are remarkably enriched in transposons. In particular, R1/R2 retrotransposons, which specifically integrate in the rDNA locus, are strongly up-regulated. Actually, depletion increases expression of transposon-inserted rDNA copies, resulting in synthesis of aberrant rRNAs and enlarged nucleolus. Concomitantly, dH1-depleted cells accumulate extra-chromosomal rDNA, show increased γH2Av content, stop proliferation and activate apoptosis, indicating that depletion causes genome instability and affects proliferation. Finally, the contributions to maintenance of genome integrity and cell proliferation appear conserved in human hH1s, as their expression rescues proliferation of dH1-depleted cells.
巻・号 40(12)
ページ 5402-14
公開日 2012-7-1
DOI 10.1093/nar/gks224
PII gks224
PMID 22406835
PMC PMC3384340
MeSH Animals Cell Proliferation Drosophila Proteins / antagonists & inhibitors Drosophila Proteins / genetics Drosophila Proteins / physiology* Drosophila melanogaster / cytology Drosophila melanogaster / genetics* Gene Expression Regulation Gene Silencing* Genome, Insect Genomic Instability* Heterochromatin / metabolism Histones / antagonists & inhibitors Histones / genetics Histones / physiology* Humans RNA Interference Retroelements*
IF 11.502
引用数 30
WOS 分野 BIOCHEMISTRY & MOLECULAR BIOLOGY
リソース情報
ショウジョウバエ 31617R-2 31617R-3