Laboratory of Biology and Modeling of the Cell (LBMC), CNRS, Ecole Normale Supérieure de Lyon, Université de Lyon, 69007 Lyon, France.
Centre de Recherche en Biologie cellulaire de Montpellier, CRBM, CNRS, University of Montpellier, 34090 Montpellier, France.
Cells. 2020 Sep 8;9(9):2049. doi: 10.3390/cells9092049.
Deposition of histone H3 lysine 4 (H3K4) methylation at promoters is catalyzed by the SET1/COMPASS complex and is associated with context-dependent effects on gene expression and local changes in chromatin organization. The role of SET1/COMPASS in shaping chromosome architecture has not been investigated. Here we used to address this question through a live imaging approach and genetic analysis. Using quantitative FRET (Förster resonance energy transfer)-based fluorescence lifetime imaging microscopy (FLIM) on germ cells expressing histones eGFP-H2B and mCherry-H2B, we find that SET1/COMPASS influences meiotic chromosome organization, with marked effects on the close proximity between nucleosomes. We further show that inactivation of , encoding the SET1 homologue, or CFP-1, encoding the chromatin targeting subunit of COMPASS, enhances germline chromosome organization defects and sterility of condensin-II depleted animals. loss also aggravates germline defects resulting from conditional inactivation of topoisomerase II, another structural component of chromosomes. Expression profiling of mutant germlines revealed only minor transcriptional changes, suggesting that the observed effects are at least partly independent of transcription. Altogether, our results are consistent with a role for SET1/COMPASS in shaping meiotic chromosomes in , together with the non-histone proteins condensin-II and topoisomerase. Given the high degree of conservation, our findings expand the range of functions attributed to COMPASS and suggest a broader role in genome organization in different species.
组蛋白 H3 赖氨酸 4（H3K4）甲基化在启动子上的沉积由 SET1/COMPASS 复合物催化，与基因表达的上下文相关效应和局部染色质组织变化有关。SET1/COMPASS 在塑造染色体结构中的作用尚未被研究。在这里，我们使用 通过活体成像方法和遗传分析来解决这个问题。通过对表达 eGFP-H2B 和 mCherry-H2B 组蛋白的生殖细胞进行定量 FRET（Förster 共振能量转移）荧光寿命成像显微镜（FLIM），我们发现 SET1/COMPASS 影响减数分裂染色体组织，对核小体之间的近距离有明显影响。我们进一步表明， 的失活，编码 SET1 同源物，或 CFP-1，编码 COMPASS 的染色质靶向亚基，增强了有condensin-II 耗尽的动物的生殖系染色体组织缺陷和不育。 缺失也加剧了由于拓扑异构酶 II（染色体的另一个结构成分）的条件性失活而导致的生殖系缺陷。 突变体生殖系的表达谱分析显示仅存在微小的转录变化，表明观察到的效应至少部分独立于转录。总之，我们的结果与 SET1/COMPASS 在塑造 减数分裂染色体中的作用一致，与非组蛋白蛋白 condensin-II 和拓扑异构酶一起。鉴于高度保守性，我们的发现扩展了 COMPASS 归因的功能范围，并表明在不同物种的基因组组织中具有更广泛的作用。
