Role of histone deacetylation in developmentally programmed DNA rearrangements in Tetrahymena thermophila
Role of histone deacetylation in developmentally programmed DNA rearrangements in Tetrahymena thermophila
复制标题
DOI：
10.1128/ec.1.2.293-303.2002
复制
发表时间：
2002-04-01
期刊：
影响因子：
--
通讯作者：
Yao, MC
中科院分区：
文献类型：
--
作者：
Duharcourt, S;Yao, MC
在四膜虫中，与其他纤毛虫一样，体细胞大核在接合过程中的发育涉及生殖系基因组的广泛和可重复的重排，包括染色体断裂和内部消除序列（ess）的切除。控制这些事件的分子机制尚不清楚。为了研究组蛋白乙酰化在这些过程中的调节作用，我们处理了与组蛋白去乙酰化酶抑制剂trichostatin A （TSA）结合的四膜虫细胞。我们发现，TSA治疗在接合的早期阶段诱导发育阻滞，但在合子核发生有丝分裂后，对接合的进展没有显著影响。观察tsa处理细胞产生的后代对IES切除和染色体断裂的影响。我们发现TSA治疗对6个IESs中5个的切除有部分抑制作用，但对4个不同位点的染色体断裂没有影响。TSA治疗大大延缓了一些细胞的发育，并抑制了大多数正在发育的大核的切除事件。它还导致通常与DNA消除相关的色域蛋白Pdd1p的特化亚核定位的丢失。我们提出了一个模型，其中乙酰化核小体标记生殖系限制序列进行切除。
In Tetrahymena, as in other ciliates, development of the somatic macronucleus during conjugation involves extensive and reproducible rearrangements of the germ line genome, including chromosome fragmentation and excision of internal eliminated sequences (IESs). The molecular mechanisms controlling these events are poorly understood. To investigate the role that histone acetylation may play in the regulation of these processes, we treated Tetrahymena cells during conjugation with the histone deacetylase inhibitor trichostatin A (TSA). We show that TSA treatment induces developmental arrests in the early stages of conjugation but does not significantly affect the progression of conjugation once the mitotic divisions of the zygotic nucleus have occurred. Progeny produced from TSA-treated cells were examined for effects on IES excision and chromosome breakage. We found that TSA treatment caused partial inhibition of excision of five out of the six IESs analyzed but did not affect chromosome breakage at four different sites. TSA treatment greatly delayed in some cells and inhibited in most the excision events in the developing macronucleus. It also led to loss of the specialized subnuclear localization of the chromodomain protein Pdd1p that is normally associated with DNA elimination. We propose a model in which underacetylated nucleosomes mark germ line-limited sequences for excision.