Targeting determinants of dosage compensation in Drosophila

被引:66
作者
Dahlsveen, Ina K.
Gilfillan, Gregor D.
Shelest, Vladimir I.
Lamm, Rosemarie
Becker, Peter B.
机构
[1] Univ Munich, Adolf Butenandt Inst, Munich, Germany
[2] RAS, Siberian Branch, Inst Laser Phys, Novosibirsk, Russia
来源
PLOS GENETICS | 2006年 / 2卷 / 02期
关键词
u;
D O I
10.1371/journal.pgen.0020005
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
The dosage compensation complex (DCC) in Drosophila melanogaster is responsible for up-regulating transcription from the single male X chromosome to equal the transcription from the two X chromosomes in females. Visualization of the DCC, a large ribonucleoprotein complex, on male larval polytene chromosomes reveals that the complex binds selectively to many interbands on the X chromosome. The targeting of the DCC is thought to be in part determined by DNA sequences that are enriched on the X. So far, lack of knowledge about DCC binding sites has prevented the identification of sequence determinants. Only three binding sites have been identified to date, but analysis of their DNA sequence did not allow the prediction of further binding sites. We have used chromatin immunoprecipitation to identify a number of new DCC binding fragments and characterized them in vivo by visualizing DCC binding to autosomal insertions of these fragments, and we have demonstrated that they possess a wide range of potential to recruit the DCC. By varying the in vivo concentration of the DCC, we provide evidence that this range of recruitment potential is due to differences in affinity of the complex to these sites. We were also able to establish that DCC binding to ectopic high-affinity sites can allow nearby low-affinity sites to recruit the complex. Using the sequences of the newly identified and previously characterized binding fragments, we have uncovered a number of short sequence motifs, which in combination may contribute to DCC recruitment. Our findings suggest that the DCC is recruited to the X via a number of binding sites of decreasing affinities, and that the presence of high-and moderate-affinity sites on the X may ensure that lower-affinity sites are occupied in a context-dependent manner. Our bioinformatics analysis suggests that DCC binding sites may be composed of variable combinations of degenerate motifs.
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页码:104 / 118
页数:15
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