Stage-resolved Hi-C analyses reveal meiotic chromosome organizational features influencing homolog alignment

Wu Zuo,Zhimei Gao,Chenhui Huang,Ming Lei,Guangming Chen,Zhengjun Chen,Shuai Li,Yanyan Chen,Qian Bian,Juan Chen

doi:10.1038/s41467-021-26033-0

Abstract

During meiosis, chromosomes exhibit dramatic changes in morphology and intranuclear positioning. How these changes influence homolog pairing, alignment, and recombination remain elusive. Using Hi-C, we systematically mapped 3D genome architecture throughout all meiotic prophase substages during mouse spermatogenesis. Our data uncover two major chromosome organizational features varying along the chromosome axis during early meiotic prophase, when homolog alignment occurs. First, transcriptionally active and inactive genomic regions form alternating domains consisting of shorter and longer chromatin loops, respectively. Second, the force-transmitting LINC complex promotes the alignment of ends of different chromosomes over a range of up to 20% of chromosome length. Both features correlate with the pattern of homolog interactions and the distribution of recombination events. Collectively, our data reveal the influences of transcription and force on meiotic chromosome structure and suggest chromosome organization may provide an infrastructure for the modulation of meiotic recombination in higher eukaryotes.

Highlights

During meiosis, chromosomes exhibit dramatic changes in morphology and intranuclear positioning
Using fluorescence-activated cell sorting (FACS) with stringent gating strategies, we isolated the somatic Sertoli cells, the rapidly proliferating spermatogonia cells, and the preleptotene cells from the testes of 7–11-day-old male C57BL/6 mice (Fig. 1a, b), the zygotene-stage spermatocytes from 2-weekold mice (Fig. 1a, c), and the pachytene and diplotene-stage spermatocytes, as well as the meiosis II (MII) spermatocytes from 3- to 5week-old mice (Fig. 1a, d)
Several recent Hi-C studies explored the functional relationships between meiotic chromosome organization and transcriptional regulation[31,32,33,34], how the highly specialized meiotic chromosome structure impacts homolog interactions and meiotic recombination is less clear

Summary

Introduction

Chromosomes exhibit dramatic changes in morphology and intranuclear positioning. The force-transmitting LINC complex promotes the alignment of ends of different chromosomes over a range of up to 20% of chromosome length Both features correlate with the pattern of homolog interactions and the distribution of recombination events. Upon re-localizing to the nuclear periphery, telomeres associate with the linker of the cytoskeleton and nucleoskeleton (LINC) complex, which transduces the force generated from the cytoskeleton to chromosomes to promote rapid chromosome movement[26,27,28] Both mechanisms are essential for homolog pairing and meiosis progression. The transcriptionally active A and inactive B compartments, though attenuated, were still present during zygotene and pachytene stages[32,34] While these studies uncovered general principles of meiotic chromosome folding, the roles of these chromosome organization features in regulating the meiotic events remain to be elucidated

Methods

Results

Conclusion