DAXX directs dual modes of H3.4-to-H3.3 histone replacement in the male germline

Genes & Development 2026 Preprint Open access

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Authors: Yu-Han Yeh, Mengwen Hu, Kai Otsuka, Brooke M. Alger, Shruti S. Nene, Han Wang, So Maezawa, Satoshi H. Namekawa
DOI: 10.1101/gad.353435.125
Cited by: 1
References: 43

Abstract

During spermatogenesis, extensive chromatin remodeling and histone replacement reshape the male germline epigenome. Although HIRA mediates transcription-coupled incorporation of histone variant H3.3, we identified DAXX as a key histone chaperone directing genome-wide, transcription-coupled replacement of H3.4 (H3T) with H3.3 on autosomes during male meiosis. Simultaneously, DAXX also directs transcription-independent H3.4-to-H3.3 replacement on the sex chromosomes during meiotic sex chromosome inactivation (MSCI). These distinct, chromosome-specific modes of DAXX-mediated H3.3 deposition are essential for epigenomic integrity in the male germline. Loss of DAXX disrupts this process, resulting in widespread transcriptional dysregulation in haploid round spermatids and impaired male fertility.

Fields of Study & Subjects

Genomics and Chromatin Dynamics Sperm and Testicular Function Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities

Publication details

Journal / source
Genes & Development
Publisher
Cold Spring Harbor Laboratory
Volume
40
Issue
11-12
Pages
796–804
Publication date
14 April 2026
Language
EN
Document type
Preprint