Non-Mendelian, heritable blocks to DNA rearrangement are induced by loading the somatic nucleus of Tetrahymena thermophila with germ line-limited DNA
Non-Mendelian, heritable blocks to DNA rearrangement are induced by loading the somatic nucleus of Tetrahymena thermophila with germ line-limited DNA
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DOI：
10.1128/mcb.16.7.3658
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发表时间：
1996-07
影响因子：
5.3
通讯作者：
D. Chalker;M. Yao
中科院分区：
文献类型：
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作者：
D. Chalker;M. Yao
在嗜热四膜虫大核发育过程中，基因组内数千个位点发生了位点特异性DNA缺失。这些缺失元件通常在大核染色体中检测不到。我们已经干扰了正常的删除这些元素中的两个，相邻的M和R元素，加载营养大核与这些元素的有性接合之前。含有外源性M或R元件的转化细胞系，携带在含有编码rRNA基因的亲本（旧）大核内的高拷贝数载体上，在形成新的大核期间始终未能切除M或R元件的染色体拷贝。观察到对相邻元件或未连接元件的缺失很少或没有干扰。每个元件的微核（生殖系）限制区足以抑制特定的DNA缺失。这种对DNA缺失的干扰通常表现为细胞质显性性状：在交配对的一个伴侣的旧大核中存在的缺失元件足以抑制另一个伴侣中发生的缺失。值得注意的是，未能切除这些元件在下一代中成为非孟德尔的可遗传性状，并且不需要外源引入元件的高拷贝数。将外源缺失元件引入亲本大核为我们提供了一种建立可遗传的DNA重排模式的表观遗传方法。
Site-specific DNA deletion occurs at thousands of sites within the genome during macronuclear development of Tetrahymena thermophila. These deletion elements are usually not detected in macronuclear chromosomes. We have interfered with the normal deletion of two of these elements, the adjacent M and R elements, by loading vegetative macronuclei with these elements prior to sexual conjugation. Transformed cell lines containing the exogenous M or R element, carried on high-copy-number vectors containing genes encoding rRNA within parental (old) macronuclei, consistently failed to excise chromosomal copies of the M or R element during formation of new macronuclei. Little or no interference with the deletions of adjacent elements or of unlinked elements was observed. The micronucleus (germ line)-limited region of each element was sufficient to inhibit specific DNA deletion. This interference with DNA deletion usually is manifested as a cytoplasmic dominant trait: deletion elements present in the old macronucleus of one partner of a mating pair were sufficient to inhibit deletion occurring in the other partner. Remarkably, the failure to excise these elements became a non-Mendelian, inheritable trait in the next generation and did not require the high copy number of exogenously introduced elements. The introduction of exogenous deletion elements into parental macronuclei provides us with an epigenetic means to establish a heritable pattern of DNA rearrangement.