Heterochromatin regulates cell type-specific long-range chromatin interactions essential for directed recombination
Heterochromatin regulates cell type-specific long-range chromatin interactions essential for directed recombination
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DOI：
10.1016/j.cell.2004.10.020
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发表时间：
2004-11-12
期刊：
影响因子：
64.5
通讯作者：
Grewal, SIS
中科院分区：
文献类型：
--
作者：
Jia, ST;Yamada, T;Grewal, SIS
粟酒裂殖酵母中的交配型转换涉及用从位于 20 kb 异染色质域内的两个沉默供体基因座（mat2-P 或 mat3-M）之一复制的序列替换表达的 mat1 基因座处的遗传信息。供体选择由细胞类型决定：mat2 是 M 细胞中的首选供体，mat3 是 P 细胞中的首选供体。在这里，我们表明，含有 Swi2 和 Swi5 蛋白的重组促进复合物 (RPC) 在沉默交配型区域表现出细胞类型特异性定位模式，并且这种差异定位在交配型转换期间调节供体偏好。在 P 细胞中，RPC 定位仅限于位于 mat3 附近的重组增强子，但在 M 细胞中，RPC 以异染色质依赖性方式顺式传播到整个沉默交配型间隔。我们的分析表明异染色质参与长期调控相互作用，并表明异染色质对交配型区域的结构组织施加影响，这对于供体选择机制很重要。
Mating-type switching in Schizosaccharomyces pombe involves replacing genetic information at the expressed mat1 locus with sequences copied from one of two silent donor loci, mat2-P or mat3-M, located within a 20-kb heterochromatic domain. Donor selection is dictated by cell type: mat2 is the preferred donor in M cells, and mat3 is the preferred donor in P cells. Here we show that a recombination-promoting complex (RPC) containing Swi2 and Swi5 proteins exhibits cell type-specific localization pattern at the silent mating-type region and this differential localization modulates donor preference during mating-type switching. In P cells, RPC localization is restricted to a recombination enhancer located adjacent to mat3, but in M cells, RPC spreads in cis across the entire silent mating-type interval in a heterochromatin-dependent manner. Our analyses implicate heterochromatin in long-range regulatory interactions and suggest that heterochromatin imposes at the mating-type region structural organization that is important for the donor-choice mechanism.