Distinct chromatin modulators regulate the formation of accessible and repressive chromatin at the fission yeast recombination hotspot ade6-m26
Distinct chromatin modulators regulate the formation of accessible and repressive chromatin at the fission yeast recombination hotspot ade6-m26
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DOI：
10.1091/mbc.e07-04-0377
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发表时间：
2008-03-01
影响因子：
3.3
通讯作者：
Ohta, Kunihiro
中科院分区：
文献类型：
--
作者：
Hirota, Kouji;Mizuno, Ken-ichi;Ohta, Kunihiro
组蛋白乙酰转移酶(HATS)和三磷酸腺苷依赖的染色质重塑因子(ADCR)通过改变局部染色质的构型来调节转录和重组。裂殖酵母的ade6-M26等位基因产生减数分裂重组热点，需要cAMP反应元件(CRE)样序列M26、atf1/PCR1异二聚体ATF/CREB转录因子、Gcn5 HAT和Snf22 SWI2/SNF2家族ADCR。染色质的改变发生在M26附近，导致减数分裂重组的激活。我们新报道了其他在M26染色质改变中起正负作用的染色质重塑因子的作用：两个CHD-1家族ADCR(Hrp1和Hrp3)，一个SPT-Ada-Gcn5乙酰转移酶组分(Ada2)，以及Moz-Ybf2/SAS3-SAS2-Tip60家族的一个成员(Mst2)。Ada2、Mst2和Hrp3是完全激活M26附近的染色质变化和减数分裂重组所必需的。在gcn5 Delta、ada2 Delta和Snf22 Delta中，组蛋白H3在M26附近的乙酰化水平显著降低，提示这些HAT复合体与Snf22具有协同作用。相反，Hrp1，另一个CHD-1家族ADCR，在ade6-m26保持抑制染色质配置。有趣的是，转录起始点从原来的起始点移动到M26附近的位置，与M26附近的组蛋白乙酰化和减数分裂染色质改变结合在一起，这表明这些染色质调节剂和转录机制之间的合作形成了可接近的染色质。这些HAT和ADCR也是调节M26周围的转录和染色质结构以响应渗透胁迫所必需的。因此，我们认为多个染色质调节剂可逆地调节染色质结构，参与Cre-like序列周围的减数分裂重组和胁迫诱导转录的调节。
Histone acetyltransferases (HATs) and ATP-dependent chromatin remodeling factors (ADCRs) regulate transcription and recombination via alteration of local chromatin configuration. The ade6-M26 allele of Schizosaccharomyces pombe creates a meiotic recombination hotspot that requires a cAMP-responsive element (CRE)-like sequence M26, the Atf1/Pcr1 heterodimeric ATF/CREB transcription factor, the Gcn5 HAT, and the Snf22 SWI2/SNF2 family ADCR. Chromatin alteration occurs meiotically around M26, leading to the activation of meiotic recombination. We newly report the roles of other chromatin remodeling factors that function positively and negatively in chromatin alteration at M26: two CHD-1 family ADCRs (Hrp1 and Hrp3), a Spt-Ada-Gcn5 acetyltransferase component (Ada2), and a member of Moz-Ybf2/Sas3-Sas2-Tip60 family (Mst2). Ada2, Mst2, and Hrp3 are required for the full activation of chromatin changes around M26 and meiotic recombination. Acetylation of histone H3 around M26 is remarkably reduced in gcn5 Delta, ada2 Delta and snf22 Delta, suggesting cooperative functions of these HAT complexes and Snf22. Conversely, Hrp1, another CHD-1 family ADCR, maintains repressive chromatin configuration at ade6-M26. Interestingly, transcriptional initiation site is shifted to a site around M26 from the original initiation sites, in couple with the histone acetylation and meiotic chromatin alteration induced around 3' region of M26, suggesting a collaboration between these chromatin modulators and the transcriptional machinery to form accessible chromatin. These HATs and ADCRs are also required for the regulation of transcription and chromatin structure around M26 in response to osmotic stress. Thus, we propose that multiple chromatin modulators regulate chromatin structure reversibly and participate in the regulation of both meiotic recombination and stress-induced transcription around CRE-like sequences.