Genomic analysis of Drosophila chromosome underreplication reveals a link between replication control and transcriptional territories

Genomic analysis of Drosophila chromosome underreplication reveals a link between replication control and transcriptional territories
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DOI:
10.1073/pnas.0502702102
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发表时间:
2005-06-07
影响因子:
11.1
通讯作者:
Zhimulev, IF
Zhimulev, IF
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Belyakin, SN;Christophides, GK;Zhimulev, IF

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在果蝇多线染色体中,大多数晚期复制区域仍然复制不足。复制不足抑制子 [Su(UR)] 基因的功能丧失突变体会抑制复制不足 (UR),而该基因的额外拷贝会增强显示 UR 的区域的水平和数量。通过将 DNA 微阵列分析与 Su(UR) 基因拷贝数操作相结合,我们实现了对 1,036 个基因的基因组规模分子鉴定,这些基因排列在 52 个 UR 染色体区域的簇中。这些区域广泛重叠 (96%),但与培养中有丝分裂 Kc 细胞的晚期复制区域并不完全相同。对已发表的基因表达谱的重新分析表明,由复制特性定义的基因组区域包括协调表达的基因簇。多线染色体中的 UR 和 Kc 细胞染色体中的晚期复制的基因组区域显示出与在睾丸/男性但不在卵巢/女性或胚胎中表达的转录区域特别常见的关联。未来测试的一个有吸引力的假设是,参与复制控制的因子,例如 SU(UR),可能与参与转录区域表观遗传沉默的因子发生物理相互作用。
In Drosophila polytene chromosomes, most late-replicating regions remain underreplicated. A loss-of-function mutant of the suppressor of underreplication [Su(UR)] gene suppresses underreplication (UR), whereas extra copies of this gene enhance the level and number of regions showing UR. By combining DNA microarray analysis with manipulation of the number of Su(UR) gene copies, we achieved genomic-scale molecular identification of 1,036 genes that are arranged in clusters located in 52 UR chromosomal regions. These regions overlap extensively (96%) but are not completely identical with late-replicating regions of mitotically dividing Kc cells in culture. Reanalysis of published gene expression profiles revealed that genomic regions defined by replication properties include clusters of coordinately expressed genes. Genomic regions that are UR in polytene chromosomes and late replicated in Kc cell chromosomes show a particularly common association with transcriptional territories that are expressed in testis/males but not ovary/females or embryos. An attractive hypothesis for future testing is that factors involved in replication control, such as SU(UR), may interact physically with those involved in epigenetic silencing of transcription territories.