High resolution maps of chromatin reorganization reveal a meiotic-specific architectural role for CTCF in mouse meiosis

Authors

• G Cheng
• F Pratto
• K Brick
• X Li
• B Alleva
• M Huang
• G Lam
• RD Camerini-Otero

Abstract

When germ cells transition from the mitotic cycle into meiotic prophase I (MPI), chromosomes condense into an array of loops that are required to promote homolog pairing and genetic recombination. To identify the changes in chromosomal conformation, we used a unique nuclei sorting strategy to isolate germ cells ranging from spermatogonia to the end of MPI. By performing Hi-C and Micro-C, we explored the chromatin reorganization at the highest resolution to date.
We found that the large-scale A/B compartmentalization was lost during MPI. Still, local subcompartments and regulatory elements interactions were maintained. This establishes a potential mechanism for how the meiotic chromatin maintains active transcription within a highly structured genome. The isolation of a rare cell population that had left spermatogonia yet not entered meiosis enabled us to uncover a concurrent decline in mitotic cohesion and a rise in meiotic cohesin before meiotic entry, which initial the meiotic chromatin reorganization. Enhanced Micro-C resolution revealed that, despite the loss of TADs, higher frequency contact between loci were detectable during MPI, coinciding with CTCF bound sites. The pattern of interactions around CTCF sites with their neighboring loci showed that CTCFs were anchoring meiotic loops. Additionally, the localization of CTCF to the meiotic axes and its interaction with meiotic-specific cohesins indicated that these anchors were at the base of loops. Strikingly, we found that double-strand break hotspot sequences interacted with CTCF bound loci at a high frequency. In summary, our high resolution data revealed previously unappreciated aspects of mammalian meiotic chromatin organization.

Scientific Focus Area: Chromosome Biology

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