Interplay between chromatin and trans-acting factors on the IME2 promoter upon induction of the gene at the onset of meiosis
Interplay between chromatin and trans-acting factors on the IME2 promoter upon induction of the gene at the onset of meiosis
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DOI：
10.1128/mcb.01661-06
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发表时间：
2007-02-01
影响因子：
5.3
通讯作者：
Tsuchiya, Eiko
中科院分区：
文献类型：
--
作者：
Inai, Tomomi;Yukawa, Masashi;Tsuchiya, Eiko
IME2基因是芽殖酵母减数分裂起始的关键调控因子之一。该基因在有丝分裂过程中通过启动子上的抑制性染色质结构受到抑制，该启动子由Rpd3-Sin3组蛋白去乙酰化酶（HDAC）复合物维持。IME2在减数分裂中的表达需要Gcn5/组蛋白乙酰转移酶、转录激活因子Ime1和染色质重塑剂RSC；然而，IME2激活的分子基础此前尚未明确。我们发现，在有丝分裂生长过程中，一个核小体掩盖了IME2的TATA元件，这种定位依赖于HDAC。这种染色质结构在减数分裂时被RSC重塑，RSC被Ime1招募到TATA。Ime1与启动子的稳定系结需要Gcn5的存在。有趣的是，在减数分裂的早期阶段，Ime1与启动子的结合水平保持在低水平，即使在启动子上Ime1和组蛋白H3乙酰化水平最高时也是如此，这使得IME2的表达比Ime1的表达延迟了4到6小时。无论IME2的转录状态如何，HDAC都持续存在于启动子中，RPD3的缺失使得IME2在IME1表达后不久表达，这表明HDAC在调节IME2表达的时间上起作用。
The IME2 gene is one of the key regulators of the initiation of meiosis in budding yeast. This gene is repressed during mitosis through the repressive chromatin structure at the promoter, which is maintained by the Rpd3-Sin3 histone deacetylase (HDAC) complex. IME2 expression in meiosis requires Gcn5/histone acetyltransferase, the transcriptional activator Ime1, and the chromatin remodeler RSC; however, the molecular basis of IME2 activation had not been previously defined. We found that, during mitotic growth, a nucleosome masked the TATA element of IME2, and this positioning depended on HDAC. This chromatin structure was remodeled at meiosis by RSC that was recruited to TATA by Ime1. Stable tethering of Ime1 to the promoter required the presence of Gcn5. Interestingly, Ime1 binding to the promoter was kept at low levels during the very early stages in meiosis, even when the levels of Ime1 and histone H3 acetylation at the promoter were at their highest, making a 4- to 6-h delay of the IME2 expression from that of IME1. HDAC was continuously present at the promoter regardless of the transcriptional condition of IME2, and deletion of RPD3 allowed the IME2 expression shortly after the expression of IME1, suggesting that HDAC plays a role in regulating the timing of IME2 expression.