Euchromatin factors HULC and Set1C affect heterochromatin organization for mating-type switching in fission yeast Schizosaccharomyces pombe

Euchromatin factors HULC and Set1C affect heterochromatin organization for mating-type switching in fission yeast Schizosaccharomyces pombe
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常染色质因子 HULC 和 Set1C 影响裂殖酵母交配型转换的异染色质组织

DOI:
10.1101/2021.03.23.436714
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发表时间:
2021
期刊:
bioRxiv
影响因子:
--
通讯作者:
Iwasaki Hiroshi
Iwasaki Hiroshi
中科院分区:
--
文献类型:
--
作者:
Chavez Alfredo Esquivel;Maki Takahisa;Tsubouchi Hideo;Handa Testuya;Kimura Hiroshi;Haber James E.;Thon Genevieve;Iwasaki Hiroshi

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裂殖酵母裂殖酵母的交配型(P或M)由转录活性mat 1盒决定,并通过使用位于相邻异染色质区域的供体mat 2或mat 3的基因转换来转换(交配型转换; MTS)。在转换过程中,遗传信息的异染色质供体基于P或M细胞类型和两个重组增强子的作用来选择,SRE 2促进使用mat 2-P,SRE 3促进使用mat 3-M,导致表达的mat 1盒的内容物的替换。最近,我们发现组蛋白H3 K4甲基转移酶复合物Set 1C参与供体选择,提出了一个问题,即一个以其在常染色质中的作用而闻名的复合物如何控制异染色质中的重组。在这里,我们报告了组蛋白H2 BK 119泛素连接酶复合物HULC在MTS中与Set 1C一起发挥功能,因为shf 1,brl 1,brl 2和rad 6基因的突变体显示出与Set 1C突变体相似的缺陷,并且与set 1 Δ属于相同的上位性组。此外,使用H3 K4 R和H2 BK 119 R组蛋白突变体和Set 1-Y897 A催化突变体,我们发现组蛋白H2 BK 119通过HULC的泛素化和组蛋白H3 K4通过Set 1C的甲基化在MTS中是功能耦合的。MTS在这些突变体中的细胞类型的偏见表明,HULC和Set 1C抑制使用的SRE 3重组增强子在M细胞中,从而有利于SRE 2和mat 2-P。与此一致,不平衡的切换在突变体中被追踪到妥协的关联的方向性因子Swi 6与重组增强子在M细胞。基于它们在其他染色体位置的已知效应,我们推测HULC和Set 1C控制核小体的移动性和SRE元件附近的链侵入。此外,我们发现HULC和Set 1C对组蛋白H3 K9甲基化和基因沉默的不同影响,与异染色质结构域中的其他功能一致。
Mating-type (P or M) of fission yeast Schizosaccharomyces pombe is determined by the transcriptionally active mat1 cassette and is switched by gene conversion using a donor, either mat2 or mat3, located in an adjacent heterochromatin region (mating-type switching; MTS). In the switching process, heterochromatic donors of genetic information are selected based on the P or M cell type and on the action of two recombination enhancers, SRE2 promoting the use of mat2-P and SRE3 promoting the use of mat3-M, leading to replacement of the content of the expressed mat1 cassette. Recently, we found that the histone H3K4 methyltransferase complex Set1C participates in donor selection, raising the question of how a complex best known for its effects in euchromatin controls recombination in heterochromatin. Here, we report that the histone H2BK119 ubiquitin ligase complex HULC functions with Set1C in MTS, as mutants in the shf1, brl1, brl2 and rad6 genes showed defects similar to Set1C mutants and belonged to the same epistasis group as set1Δ. Moreover, using H3K4R and H2BK119R histone mutants and a Set1-Y897A catalytic mutant, we found that ubiquitylation of histone H2BK119 by HULC and methylation of histone H3K4 by Set1C are functionally coupled in MTS. Cell-type biases in MTS in these mutants suggested that HULC and Set1C inhibit the use of the SRE3 recombination enhancer in M cells, thus favoring SRE2 and mat2-P. Consistent with this, imbalanced switching in the mutants was traced to compromised association of the directionality factor Swi6 with the recombination enhancers in M cells. Based on their known effects at other chromosomal locations, we speculate that HULC and Set1C control nucleosome mobility and strand invasion near the SRE elements. In addition, we uncovered distinct effects of HULC and Set1C on histone H3K9 methylation and gene silencing, consistent with additional functions in the heterochromatic domain.
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