Developmental control of gene copy number by repression of replication initiation and fork progression.
Developmental control of gene copy number by repression of replication initiation and fork progression.
复制标题
通过抑制复制起始和分叉进展来控制基因拷贝数。
DOI：
10.1101/gr.126003.111
复制
发表时间：
2012
期刊：
影响因子：
7
通讯作者：
Orr-Weaver,TerryL
中科院分区：
文献类型：
--
作者：
Sher,Noa;Bell,GeorgeW;Li,Sharon;Nordman,Jared;Eng,Thomas;Eaton,MatthewL;Macalpine,DavidM;Orr-Weaver,TerryL
Precise DNA replication is crucial for genome maintenance, yet this process has been inherently difficult to study on a genome-wide level in untransformed differentiated metazoan cells. To determine how metazoan DNA replication can be repressed, we examined regions selectively under-replicated inDrosophilapolytene salivary glands, and found they are transcriptionally silent and enriched for the repressive H3K27me3 mark. In the first genome-wide analysis of binding of the origin recognition complex (ORC) in a differentiated metazoan tissue, we find that ORC binding is dramatically reduced within these large domains, suggesting reduced initiation as one mechanism leading to under-replication. Inhibition of replication fork progression by the chromatin protein SUUR is an additional repression mechanism to reduce copy number. Although repressive histone marks are removed when SUUR is mutated and copy number restored, neither transcription nor ORC binding is reinstated. Tethering of the SUUR protein to a specific site is insufficient to block replication, however. These results establish that developmental control of DNA replication, at both the initiation and elongation stages, is a mechanism to change gene copy number during differentiation.
