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异染色质调控细胞类型特异性的远距离染色质相互作用,这对于定向重组至关重要。

Heterochromatin regulates cell type-specific long-range chromatin interactions essential for directed recombination.

作者信息

Jia Songtao, Yamada Takatomi, Grewal Shiv I S

机构信息

Laboratory of Molecular Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.

出版信息

Cell. 2004 Nov 12;119(4):469-80. doi: 10.1016/j.cell.2004.10.020.

Abstract

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.

摘要

粟酒裂殖酵母中的交配型转换涉及用从位于20 kb异染色质结构域内的两个沉默供体位点之一(mat2-P或mat3-M)复制的序列替换表达的mat1位点处的遗传信息。供体选择由细胞类型决定:mat2是M细胞中的首选供体,而mat3是P细胞中的首选供体。在这里,我们表明,包含Swi2和Swi5蛋白的重组促进复合物(RPC)在沉默交配型区域呈现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过程中调节供体偏好。在P细胞中,RPC定位局限于与mat3相邻的重组增强子,但在M细胞中,RPC以异染色质依赖性方式顺式扩散穿过整个沉默交配型间隔。我们的分析表明异染色质参与远程调控相互作用,并表明异染色质在交配型区域施加了对供体选择机制很重要的结构组织。

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