Multifaceted Roles of Histone Lysine Lactylation in Meiotic Gene Dynamics and Recombination
Year: 2024
Type: preprint
Abstract: Male germ cells, which are responsible for producing millions of genetically diverse sperm through meiosis in the testis, rely on lactate as their central energy metabolite. Recent study has revealed that lactate induces epigenetic modification in cells through histone lactylation, a post-translational modification involving the addition of lactyl groups to lysine residues on histones. Here we report dynamic histone lactylation at histone H4-lysine 5 (K5), -K8, and -K12 during meiosis prophase I in mouse spermatogenesis. By profiling genome-wide occupancy of histone H4-K8 lactylation (H4K8la), which peaks at zygotene, our data show that H4K8la mark is observed at the promoters of genes exhibiting active expression with Gene Ontology (GO) functions enriched for meiosis. Notably, our data also demonstrate that H4K8la is closely associated with recombination hotspots, where machinery involved in the processing DNA double-stranded breaks (DSBs), such as SPO11, DMC1, RAD51, and RPA2, is engaged. In addition, H4K8la was also detected at the meiosis-specific cohesion sites (marked by RAD21L and REC8) flanking the recombination hotspots. Collectively, our findings suggest that histone lactylation serves as a novel mechanism through which lactate regulates germ cell meiosis.
Authors: Xiaoyu Zhang, Yan Liu, Ning Wang
Institution: University of Kansas Medical Center
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
Awards: G2853296776, Defining the Mechanism of Meiotic Initiation Through Autophagy Pathway, G2921881625, G3882243453, G4924162002, High Throughput Sequencing System for KUMC Genomics Core, G5971186999, G7285114270, G7715825839, G8105284078, G9000049655, G9000078445, Frontiers Clinical and Translational Science Institute at the University of Kansas, G9000150948, Kansas IDeA Network of Biomedical Research Excellence 5
OpenAlex ID: W4391281839