REC8-cohesin, chromatin and transcription orchestrate meiotic recombination in the Arabidopsis genome

REC8-cohesin, chromatin and transcription orchestrate meiotic recombination in the Arabidopsis genome
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REC8-粘连蛋白、染色质和转录协调拟南芥基因组中的减数分裂重组

DOI:
10.1101/512400
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发表时间:
2019
期刊:
--
影响因子:
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通讯作者:
Lambing C
Lambing C
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作者:
Lambing C

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在减数分裂期间,染色体经历DNA双链断裂(DSB),可以使用同源物进行修复以产生交叉,从而产生遗传多样性。减数分裂重组与同源配对和减数分裂轴与联会复合体(SC)的聚合同时发生。REC 8-粘附素是连接染色体到轴和组织轴聚合所必需的。然而,REC 8沿沿着染色体装载的控制,与染色质、转录和重组有关,尚未完全理解。因此,我们在拟南芥中进行了REC 8 ChIP-seq,其揭示了着丝粒异染色质的强烈富集。REC 8丰度与减数分裂DSB和交换的抑制相关,尽管轴负载SPO 11 -1在这些地区。异染色质标记H3 K9 me 2和非CG DNA甲基化inkyp/suvh 4 suvh 5 suvh 6突变体的丢失导致REC 8的重塑和重复序列中局部减数分裂重组的获得,尽管着丝粒凝聚力得以维持。在染色体臂中,REC 8在基因体、外显子和富含GC的序列中富集,并且与转录反相关。最高的REC 8占有率发生在系留沉默的H3 K27 me 3修饰的基因中。使用免疫细胞学,我们表明,轴polycomplex形成inrec 8突变体,招募重组灶改变化学计量,导致灾难性的非同源重组。因此,REC 8在组织减数分裂染色体结构和促进高保真同源重组中起着关键作用。尽管有这种促重组作用,但局部REC 8富集与精细尺度下的DSB阻遏相关,这与栓系环/轴模型一致。与其在减数分裂过程中的组织作用相一致,REC 8-粘附素沿着染色体的占据沿着由多个染色质状态和转录形成。
During meiosis chromosomes undergo DNA double-strand breaks (DSBs) that can be repaired using a homolog to produce crossovers, which creates genetic diversity. Meiotic recombination occurs coincident with homolog pairing and polymerization of the meiotic axis and synaptonemal complex (SC). REC8-cohesin is required to connect chromosomes to the axis and to organize axis polymerization. However, control of REC8 loading along chromosomes, in relation to chromatin, transcription and recombination, is not yet fully understood. Therefore, we performed REC8 ChIP-seq in Arabidopsis, which revealed strong enrichment in centromeric heterochromatin. REC8 abundance correlates with suppression of meiotic DSBs and crossovers, despite axis loading of SPO11-1 in these regions. Loss of the heterochromatic marks H3K9me2 and non-CG DNA methylation inkyp/suvh4 suvh5 suvh6mutants causes remodeling of REC8 and gain of meiotic recombination locally in repeated sequences, although centromere cohesion is maintained. In the chromosome arms, REC8 is enriched within gene bodies, exons and GC-rich sequences, and anti-correlates with transcription. Highest REC8 occupancy occurred in facultatively silent, H3K27me3-modified genes. Using immunocytology we show that axis polycomplexes form inrec8mutants that recruit recombination foci with altered stoichiometry, leading to catastrophic non-homologous recombination. Therefore, REC8 plays a key role organizing meiotic chromosome architecture and promoting high-fidelity interhomolog recombination. Despite this pro-recombination role, local REC8 enrichment associates with DSB repression at the fine scale, which is consistent with the tethered-loop/axis model. Coincident with its organizational role during meiosis, REC8-cohesin occupancy along the chromosomes is shaped by multiple chromatin states and transcription.
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