Chromosome-wide gene-specific targeting of the Drosophila dosage compensation complex
Chromosome-wide gene-specific targeting of the Drosophila dosage compensation complex
复制标题
DOI：
10.1101/gad.1399406
复制
发表时间：
2006-04-01
影响因子：
10.5
通讯作者：
Becker, PB
中科院分区：
文献类型：
--
作者：
Gilfillan, GD;Straub, T;Becker, PB
黑腹果蝇的剂量补偿复合体（DCC）能够区分细胞核中的单条雄性X染色体与其他染色体。它以不连续的模式与X染色体的大部分区域选择性地相互作用。DCC如何识别并结合X染色体，包括结合众多需要剂量补偿的基因，目前尚不清楚。为了鉴定被结合的基因并尝试分离靶向信号，我们通过将染色质免疫沉淀与高分辨率微阵列技术相结合，观察了雄性特异性致死1（MSL1）蛋白沿X染色体的结合情况。观察到DCC有700多个结合区域，涵盖了X染色体上一半以上的基因。此外，还鉴定出了几个罕见的常染色体结合位点。必需基因是优先的靶标，结合高水平DCC的基因似乎经历了最多的补偿（即表达量增加最多）。DCC结合明显倾向于基因而非基因间区域，并且最强地结合到转录单位的3'端。在靶向基因内，DCC对 exon（外显子）和编码序列表现出强烈的偏好。我们的结果证明了DCC的基因特异性结合，并确定了几个可能部分指导其靶向的序列元件。
The dosage compensation complex (DCC) of Drosophila melanogaster is capable of distinguishing the single male X from the other chromosomes in the nucleus. it selectively interacts in a discontinuous pattern with much of the X chromosome. How the DCC identifies and binds the X, including binding to the many genes that require dosage compensation, is currently unknown. To identify bound genes and attempt to isolate the targeting cues, we visualized male-specific lethal 1 (MSL1) protein binding along the X chromosome by combining chromatin immunoprecipitation with high-resolution microarrays. More than 700 binding regions for the DCC were observed, encompassing more than half the genes found on the X chromosome. In addition, several rare autosomal binding sites were identified. Essential genes are preferred targets, and genes binding high levels of DCC appear to experience the most compensation (i.e., greatest increase in expression). DCC binding clearly favors genes over intergenic regions, and binds most strongly to the 3 ' end of transcription units. Within the targeted genes, the DCC exhibits a strong preference for exons and coding sequences. Our results demonstrate gene-specific binding of the DCC, and identify several sequence elements that may partly direct its targeting.