Super-resolution imaging reveals structurally distinct periodic patterns of chromatin along pachytene chromosomes
Kirti Prakash, David Fournier, Stefan Redl, Gerrit Best, Máté Borsos, René Ketting, KiKuë Tachibana-Konwalski, Christoph Cremer, Udo Birk
Abstract
During meiosis, homologous chromosomes associate to form a unique structure called synaptonemal complex (SC) whose disruption leads to infertility. Information about the epigenetic features of chromatin within this structure at the level of super-resolution microscopy is largely lacking. We combined single molecule localization microscopy with quantitative analytical methods to describe the epigenetic landscape of meiotic chromosomes at the pachytene stage in mouse oocytes. DNA is found to be non-randomly distributed along the length of the SC in condensed clusters. Periodic clusters of repressive chromatin (trimethylation of histone H3 at lysine 27, H3K27me3) are found at 500 nm intervals along the SC, while one of the ends of SC displays a large and dense cluster of centromeric histone mark (trimethylation of histone H3 at lysine 9, H3K9me3). Chromatin associated with active transcription (trimethylation of histone H3 at lysine 4, H3K4me3) is arranged in a radial hair-like loop pattern emerging laterally from the SC. These loops seem to be punctuated with small clusters of H3K4me3 mark with an average spread larger than their spacing. Our findings indicate that the nanoscale structure of the pachytene chromosomes is constrained by periodic patterns of chromatin marks, whose function in recombination and higher-order genome organisation is yet to be elucidated.
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