BPS2026 – Tissue-specific profiling reveals compaction of meiotic chromosomes

Meiosis is essential for sexual reproduction since it enables production of haploid gametes from diploid precursors. At meiotic entry, chromosomes undergo dramatic remodeling to form linear arrays of chromatin loops that emanate from a cohesin-enriched proteinaceous axis. The length of individual loops has been estimated to be 0.2–1 Mb in different organisms, but the organization of chromatin within loops has not been well-characterized. We have optimized tissue-specific chromatin profiling using CUT&RUN and CUT&Tag in C. elegans , which revealed unexpected signatures of meiotic chromosome compaction. When we used CUT&RUN and CUT&Tag to generate genome-wide profiles of histone modifications, we observed both method-dependent and tissue-specific differences. In intestinal nuclei, these two methods produced largely concordant profiles, although the signal-to-background was generally higher for CUT&Tag. In germline nuclei, however, CUT&RUN peaks were consistently broader than CUT&Tag for several different histone marks. We interpret this broadening as an indication of chromatin compaction, such that tethered enzymes reach further along the chromatin fiber. We believe that the effect is more pronounced for CUT&RUN because it uses an enzyme (MNase) that can make multiple cuts, whereas the Tn5 transposase used in CUT&Tag can only “tagment” DNA once. CUT&RUN profiles therefore capture cumulative cleavage events until the reaction is stopped. This germline-specific spreading implies that nucleosomes are more closely packed in meiotic chromosomes than interphase chromatin. Importantly, the degree of spreading suggests compaction on a sub-kb scale, which would be difficult to detect with chromosome conformation capture methods. We are now investigating the molecular mechanisms driving meiotic chromosome compaction and how chromosome architecture contributes to meiotic recombination and to reproductive success.