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CTCF-mediated 3D chromatin sets up the gene expression program in the male germline.
Nat Struct Mol Biol
March 2025
Department of Microbiology and Molecular Genetics, University of California, Davis, CA, USA.
Spermatogenesis is a unidirectional differentiation process that generates haploid sperm, but how the gene expression program that directs this process is established is largely unknown. Here we determine the high-resolution three-dimensional (3D) chromatin architecture of mouse male germ cells during spermatogenesis and show that CTCF-mediated 3D chromatin dictates the gene expression program required for spermatogenesis. In undifferentiated spermatogonia, CTCF-mediated chromatin interactions between meiosis-specific super-enhancers (SEs) and their target genes precede activation of these SEs on autosomes.
View Article and Find Full Text PDFPositioning of sperm tail longitudinal columns depend on Nsun7, an RNA binding protein destabilizing elongated spermatid transcripts.
RNA
March 2025
Center of Molecular and Cellular Biology, Skolkovo Institute of Science and Technology; Belozersky Institute of Physico-Chemical Biology and Faculty of Chemistry, Lomonosov Moscow State University
Spermatozoid's flagella assemble in transcriptionally silent spermatids and thus depends on post-transcriptional regulation of gene expression. Mutations in Nsun7 gene are known to cause male infertility in human and mice. We identified m5C-specific Nsun7 RNA methyltransferase as a protein present in elongated spermatids and interacting with RNAs specific for this type of spermatozoid's precursor cells.
View Article and Find Full Text PDFMale germ cells with Bag5 deficiency show reduced spermiogenesis and exchange of basic nuclear proteins.
Cell Mol Life Sci
February 2025
Department of Obstetrics and Gynecology, Perinatal Medical Center, The Fifth Affiliated Hospital of Sun Yat-Sen University, No. 52 Meihua East Road, Zhuhai, Guangdong, People's Republic of China.
Bcl-2 associated athanogene-5 (BAG5) represents a unique BAG cochaperone family member, regulating chaperone activity. We first demonstrated significant differences in Bag5 expression by RNA seq analysis of teratozoospermia and healthy male sperm samples, but the genetic and molecular mechanisms governing this process remain elusive. We further found that BAG5 has highest expression in human and mouse testes.
View Article and Find Full Text PDFRedox signaling regulation in human spermatozoa: a primary role of peroxiredoxins.
Asian J Androl
February 2025
Department of Surgery (Urology Division), Faculty of Medicine and Health Sciences, McGill University, Montréal, QC H4A 3J1, Canada.
Reactive oxygen species (ROS) play a dual role in mammalian spermatozoa. At high levels, they are detrimental to sperm function since they can promote oxidative stress that produces oxidation of protein, lipids, and sperm DNA. This oxidative damage is associated with male infertility.
View Article and Find Full Text PDFChromatin environment-dependent effects of DOT1L on gene expression in male germ cells.
Commun Biol
January 2025
Université Paris Cité, CNRS, Inserm, Institut Cochin, F-75014, Paris, France.
The H3K79 methyltransferase DOT1L is essential for multiple aspects of mammalian development where it has been shown to regulate gene expression. Here, by producing and integrating epigenomic and spike-in RNA-seq data, we decipher the molecular role of DOT1L during mouse spermatogenesis and show that it has opposite effects on gene expression depending on chromatin environment. On one hand, DOT1L represses autosomal genes that are devoid of H3K79me2 at their bodies and located in H3K27me3-rich/H3K27ac-poor environments.
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