Meiotic chromatin-associated HSF5 is indispensable for pachynema progression and male fertility

Abstract

The pachynema progression, a crucial meiotic process, contributes to the completion of prophase I. Nevertheless, the regulation of this significant meiotic process remains poorly understood. In this study, we identified a novel testis-specific protein HSF5, which regulates pachynema progression during male meiosis in a chromatin-binding manner. Deficiency of HSF5 results in meiotic arrest and male infertility, characterized as unconventionally accumulated pachynema halting at the mid-to-late stage, with extensive spermatocyte apoptosis. Our scRNA-seq data confirmed consistent expressional alterations of certain driver genes(Sycp1, Msh4, Meiob, etc.) crucial for pachynema progression in Hsf5-/- individuals. Ulteriorly, HSF5 was revealed to primarily bind to promoter regions of such key divers by CUT&Tag analysis. Also, our results demonstrated that HSF5 biologically interacted with the chromatin-remodeling SWI/SNF complex, and it could function as a transcriptional factor for pachynema progression during meiosis. Therefore, our study underscores the importance of the chromatin-associated HSF5 for the differentiation of spermatocytes, improving the protein regulatory network of the pachynema progression.

Instructions for this dataset

The source code required to reproduce the single-cell analysis results of the article is provided, and intermediate files in the analysis are also provided. The intermediate file is a filtered and manually annotated Seurat object that can be read directly by R. Raw reads of the single-cell data can be found at NCBI SRA repository PRJNA1098350. The two tables are the raw data of the mass spectrometry-based proteomics.

Seurat_analysis.R: R code to reproduce the single cell analysis results in the article.

scvelo_analysis.py: Python code to reproduce the single-cell RNA velocity analysis results in the article.

Whole_testis.rds, Germ_cells.rds: Seurat objects stored in rds format contain whole testis cells and sperm cells respectively.