Drosophila melanogaster linker histone dH1 is required for transposon silencing and to preserve genome integrity.
Drosophila melanogaster linker histone dH1 is required for transposon silencing and to preserve genome integrity.
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DOI：
10.1093/nar/gks224
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发表时间：
2012-07
影响因子：
14.9
通讯作者：
Azorín F
中科院分区：
文献类型：
--
作者：
Vujatovic O;Zaragoza K;Vaquero A;Reina O;Bernués J;Azorín F
组蛋白H1是染色质的内在组成部分，其对染色质结构的重要贡献在体外已得到证实。然而，对其在体内的功能作用知之甚少。在这里，我们在果蝇中解决了这个问题，因为它包含一个单一的dH 1变体，所以这个模型系统提供了许多优势。为此，RNAi被用于有效地消耗果蝇中的dH 1。表达谱分析表明，dH 1消耗影响表达的一个相对较小的基因在一个区域的方式。此外，耗竭上调非活性基因，优先那些位于异染色质，而活性常染色质基因下调，这表明DH 1的转录调控的贡献主要是结构，组织染色质适当的基因表达调控。上调基因在转座子中显著富集。特别是，R1/R2反转录转座子，其特异性地整合在rDNA基因座中，被强烈上调。事实上，消耗增加转座子插入的rDNA拷贝的表达，导致异常rRNA的合成和核仁扩大。同时，dH 1耗尽的细胞积累染色体外rDNA，显示增加的γ H2 Av含量，停止增殖并激活凋亡，表明耗尽导致基因组不稳定并影响增殖。最后，对维持基因组完整性和细胞增殖的贡献似乎在人hH 1 s中是保守的，因为它们的表达挽救了dH 1耗尽细胞的增殖。
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.
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影响因子：
12.3
作者：
Gentleman RC;Carey VJ;Bates DM;Bolstad B;Dettling M;Dudoit S;Ellis B;Gautier L;Ge Y;Gentry J;Hornik K;Hothorn T;Huber W;Iacus S;Irizarry R;Leisch F;Li C;Maechler M;Rossini AJ;Sawitzki G;Smith C;Smyth G;Tierney L;Yang JY;Zhang J
通讯作者：
Zhang J
影响因子：
1.5
作者：
Fanti, L;Berloco, M;Pimpinelli, S
通讯作者：
Pimpinelli, S
影响因子：
5.3
作者：
Fan, YH;Nikitina, T;Skoultchi, AI
通讯作者：
Skoultchi, AI
影响因子：
4.8
作者：
Hellauer, K;Sirard, E;Turcotte, B
通讯作者：
Turcotte, B
影响因子：
11.4
作者：
Braunschweig, Ulrich;Hogan, Greg J.;van Steensel, Bas
通讯作者：
van Steensel, Bas