Inheritance of Polycomb-dependent chromosomal interactions in Drosophila
Inheritance of Polycomb-dependent chromosomal interactions in Drosophila
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DOI：
10.1101/gad.269503
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发表时间：
2003-10-01
影响因子：
10.5
通讯作者：
Cavalli, G
中科院分区：
文献类型：
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作者：
Bantignies, F;Grimaud, C;Cavalli, G
维持细胞身份是一项复杂的任务，涉及多层调控，作用于染色质包装的所有水平，从核小体到细胞核中染色体结构域的折叠。多梳组（PcG）和三胸组（trxG）蛋白通过与称为PcG反应元件或细胞记忆模块的顺式调节元件结合来维持染色质状态的记忆。Fab-7是一个明确的细胞记忆模块，参与调控同源异型基因Abdominal-B（Abd-B）。除了其顺式作用外，我们还通过三维FISH显示，Fab-7元件导致转基因相互关联或与内源性Fab-7关联，即使插入不同的染色体中。这些长距离相互作用增强了PcG介导的沉默。它们依赖于PcG蛋白、DNA序列同源性和发育进程。一旦通过去除内源性Fab-7消除长距离配对，在转基因基因座处诱导的去阻遏的染色质状态可以通过减数分裂传递到大部分子代中，甚至在重新引入内源性Fab-7之后。引人注目的是，去阻遏状态的减数分裂遗传涉及内源性和转基因Fab-7之间配对的丧失。这表明，通过细胞分裂的核结构的传输可能有助于在真核生物中的染色质状态的遗传。
Maintenance of cell identity is a complex task that involves multiple layers of regulation, acting at all levels of chromatin packaging, from nucleosomes to folding of chromosomal domains in the cell nucleus. Polycomb-group (PcG) and trithorax-group (trxG) proteins maintain memory of chromatin states through binding at cis-regulatory elements named PcG response elements or cellular memory modules. Fab-7 is a well-defined cellular memory module involved in regulation of the homeotic gene Abdominal-B (Abd-B). In addition to its action in cis, we show here by three-dimensional FISH that the Fab-7 element leads to association of transgenes with each other or with the endogenous Fab-7, even when inserted in different chromosomes. These long-distance interactions enhance PcG-mediated silencing. They depend on PcG proteins, on DNA sequence homology, and on developmental progression. Once long-distance pairing is abolished by removal of the endogenous Fab-7, the derepressed chromatin state induced at the transgene locus can be transmitted through meiosis into a large fraction of the progeny, even after reintroduction of the endogenous Fab-7. Strikingly, meiotic inheritance of the derepressed state involves loss of pairing between endogenous and transgenic Fab-7. This suggests that transmission of nuclear architecture through cell division might contribute to inheritance of chromatin states in eukaryotes.