ArticleClinical epigenetics2021
Epigenetic landscape of testis specific histone H2B variant and its influence on sperm function.
Article in Clinical epigenetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 21 citations in OpenAlex.
- Higher-order genome architecture of spermatids guides chromatin assembly in mature sperm.Research square · 2026Article
- Integrated fetal testicular transcriptomic and epigenomic profiles during maternal nutrient restriction with dietary melatonin intervention.Journal of animal science · 2026Article
- H2B.W2, a spermatocyte-specific histone variant, disrupts nucleosome stability, and reduces chromatin compaction.Nucleic acids research · 2025Article
- Unmasking the Epigenome: Insights into Testicular Cell Dynamics and Reproductive Function.International journal of molecular sciences · 2025Review
- The ABCs of the H2Bs: The histone H2B sequences, variants, and modifications.Trends in genetics : TIG · 2025Review
- Autism-RelatedBiomolecules · 2024Article
- Casting histone variants during mammalian reproduction.Chromosoma · 2023Review
- R-loop landscape in mature human sperm: Regulatory and evolutionary implications.Frontiers in genetics · 2023Article
- Underestimated Aspects in Male Infertility: Epigenetics is A New Approach in Men with Obesity or Diabetes: A Review.International journal of fertility & sterility · 2022Article
- Heterogeneity in the Epigenetic Landscape of Murine Testis-Specific Histone Variants TH2A and TH2B Sharing the Same Bi-Directional Promoter.Frontiers in cell and developmental biology · 2021Article
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4 authors at 1 institution in 1 country.
Funding
Abstract
backgroundBiological relevance of the major testis specific histone H2B variant (TH2B) in sperm is not fully understood. Studies in TH2A/TH2B double knockout male mice indicate its role in chromatin compaction and male fertility. Additionally, the presence of TH2B and TH2A reportedly generates more dynamic nucleosomes, leading to an open chromatin structure characteristic of transcriptionally active genome. Given that mature human sperm are transcriptionally and translationally inactive, the presence of TH2B in mature sperm is intriguing. To address its role in sperm, we investigated the genome-wide localization of TH2B in sperm of fertile men.
resultsWe have identified the genomic loci associated with TH2B in fertile human sperm by ChIP-seq analysis. Bioinformatic analysis revealed ~ 5% sperm genome and 5527 genes to be associated with TH2B. Out of these 105 (1.9%) and 144 (2.6%) genes showed direct involvement in sperm function and early embryogenesis, respectively. Chromosome wide analysis for TH2B distribution indicated its least distribution on X and Y chromosomes and varied distribution on autosomes. TH2B showed relatively higher percentage of gene association on chromosome 4, 18, 3 and 2. TH2B enrichment was more in promoter and gene body region. Gene Ontology (GO) analysis revealed signal transduction and associated kinase activity as the most enriched biological and molecular function, respectively. We also observed the enrichment of TH2B at developmentally important loci, such as HOXA and HOXD and on genes required for normal sperm function, few of which were validated by ChIP-qPCR. The relative expression of these genes was altered in particular subgroup of infertile men showing abnormal chromatin packaging. Chromatin compaction positively correlated with sperm- motility, concentration, viability and with transcript levels of PRKAG2 and CATSPER B.
conclusionChIP-seq analysis of TH2B revealed a putative role of TH2B in sperm function and embryo development. Altered expression of TH2B associated genes in infertile individuals with sperm chromatin compaction defects indicates involvement of TH2B in transcriptional regulation of these genes in post meiotic male germ cells. This altered transcriptome may be a consequence or cause of abnormal nuclear remodeling during spermiogenesis.
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