High-resolution chromatin mapping reveals that CTCF anchors meiotic loops to the chromosome axis

Abstract

When precursor germ cells enter meiosis, chromosomes condense into an array of chromatin loops. Using Hi-C and Micro-C, we explored the trajectory of chromatin reorganization from mouse spermatogonia to spermatocytes at the highest temporal and spatial resolution to date. We show that meiotic chromatin reorganization, characterized by a shift from mitotic-to-meiotic cohesins, precedes the traditionally defined meiotic entry point (meiotic G1/S-phase). We find that large-scale A/B compartments are lost during prophase I, while local sub-compartments and interactions between regulatory elements of gene expression remain. For the first time, we detect distinct looping positions in mammalian meiosis I prophase. These loops are anchored by a subset of CTCF sites at the base of chromatin loops but formed without enriched interactions within the intervening regions, deviating from the typical pattern observed in somatic interphase cells. Our findings allow us to reconcile the current discrepancy in the length of meiotic chromatin loops and support a model where meiotic loops are formed by association of existing loops modulated by CTCF rather than by loop extrusion. Here, the authors use high-resolution chromatin contact maps from mouse sperm precursors to reveal an intermediate folding state for chromosomes prior to meiotic entry and identify distinct looping positions associated with CTCF.