Abstract
Cohesin organizes the genome by forming intra-chromosomal loops and inter-sister chromatid linkages. During gamete formation by meiosis, chromosomes are reshaped to support crossover recombination and two consecutive rounds of chromosome segregation. Here we show that meiotic chromosomes are organised into functional domains by Eco1 acetyltransferase-dependent positioning of both chromatin loops and sister chromatid cohesion in budding yeast. Eco1 acetylates the Smc3 cohesin subunit in meiotic S phase to establish chromatin boundaries, independently of DNA replication. Boundary formation by Eco1 is critical for prophase exit and for the maintenance of cohesion until meiosis II, but is independent of the ability of Eco1 to antagonize the cohesin-release factor, Wpl1. Conversely, prevention of cohesin release by Wpl1 is essential for centromeric cohesion, kinetochore monoorientation and co-segregation of sister chromatids in meiosis I. Our findings establish Eco1 as a key determinant of chromatin boundaries and cohesion positioning, revealing how local chromosome structuring directs genome transmission into gametes.
Highlights
The cohesin complex defines genome architecture to support DNA repair, gene expression and chromosome segregation (Davidson and Peters, 2021)
We further note that Eco1-dependent loop stabilization critically defines the boundaries that demarcate the pericentromeric domain. This is consistent with the greater requirement of Eco[1] to maintain cohesin association with borders and chromosomal arm sites (Figure 3). 309 Boundaries are formed de-novo in meiosis in a manner independent on DNA replication Our findings show that Eco[1] is a key determinant of loop anchors at pericentromere borders and other chromosomal boundaries in meiotic prophase cells
The contact stripe originating from centromeres was diminished in clb[5] clb[6] and accompanied by a loss of centromeric insulation (Figure 6-figure supplement 1D and F) suggesting that Clb[5] and Clb[6] promote centromere-anchored loop extrusion, though the mechanism is unclear. These results indicate that loop extrusion and boundary establishment occur independently of DNA replication but that DNA replication itself, or another S phase CDK-dependent process, boosts loop formation and anchoring. 351 Replication-independent Smc[3] acetylation defines meiotic chromosome loops The fact that DNA replication is required neither for the formation of boundaries nor for Eco1-dependent acetylation of cohesin suggested that Eco[1] could form loop anchors by directly acetylating loop-extruding cohesin complexes, rather than complexes engaged in cohesion
Summary
The cohesin complex defines genome architecture to support DNA repair, gene expression and chromosome segregation (Davidson and Peters, 2021). 351 Replication-independent Smc[3] acetylation defines meiotic chromosome loops The fact that DNA replication is required neither for the formation of boundaries nor for Eco1-dependent acetylation of cohesin suggested that Eco[1] could form loop anchors by directly acetylating loop-extruding cohesin complexes, rather than complexes engaged in cohesion To test this idea, we compared the effects of Eco[1 356] on cohesin distribution and chromosome conformation in prophase-arrested 357 unreplicated and replicated cells. Eco[1] acetylation of Smc[3] is essential for prophase exit and sister chromatid segregation in meiosis II, even in the absence of Wpl[1], likely due to its requirement for cohesin anchoring to establish chromatin boundaries
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