ArticleGenome biology2019
Gene editing of the multi-copy H2A.B gene and its importance for fertility.
Article in Genome biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 38 citations in OpenAlex.
- Distinct functions in fertility and patterns of paternal incorporation of the histone H2A variants HTAS-1 and HTZ-1 in C. elegans.Genetics · 2026Article
- Dynamic architecture of mammalian paternal chromatin: histone-to-protamine exchange and post-fertilization reprogramming.Epigenetics & chromatin · 2025Review
- Epigenetic regulation by DNA methylation, histone modifications and chromatin remodeling complexes in controlling spermatogenesis and their dysfunction with male infertility.Cellular and molecular life sciences : CMLS · 2025Review
- Nonchromatin regulatory functions of the histone variant H2A.B in SWI/SNF genomic deposition.Science advances · 2025Article
- TheBiomolecules · 2025Review
- Multifunctional histone variants in genome function.Nature reviews. Genetics · 2025Review
- The Function of H2A Histone Variants and Their Roles in Diseases.Biomolecules · 2024Review
- Bull Sperm SWATH-MS-Based Proteomics Reveals Link between High Fertility and Energy Production, Motility Structures, and Sperm-Oocyte Interaction.Journal of proteome research · 2023Article
- Casting histone variants during mammalian reproduction.Chromosoma · 2023Review
- Histone Variants and Their Chaperones in Hematological Malignancies.HemaSphere · 2023Review
- Nucleosomes in mammalian sperm: conveying paternal epigenetic inheritance or subject to reprogramming between generations?Current opinion in genetics & development · 2023Review
- ThroughoutFrontiers in endocrinology · 2023Article
- A standardized nomenclature for mammalian histone genes.Epigenetics & chromatin · 2022Review
- Histone variants: The unsung guardians of the genome.DNA repair · 2022Review
- H2A.B is a cancer/testis factor involved in the activation of ribosome biogenesis in Hodgkin lymphoma.EMBO reports · 2021Article
- Effects of H2A.B incorporation on nucleosome structures and dynamics.Biophysical journal · 2021Article
- Histone variants at a glance.Journal of cell science · 2021Review
- Mini-Review Regarding the Applicability of Genome Editing Techniques Developed for Studying Infertility.Diagnostics (Basel, Switzerland) · 2021Review
- Short H2A histone variants are expressed in cancer.Nature communications · 2021Article
- Disease gene discovery in male infertility: past, present and future.Human genetics · 2021Review
Corrections and comments
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Authors and funding
11 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAltering the biochemical makeup of chromatin by the incorporation of histone variants during development represents a key mechanism in regulating gene expression. The histone variant H2A.B, H2A.B.3 in mice, appeared late in evolution and is most highly expressed in the testis. In the mouse, it is encoded by three different genes. H2A.B expression is spatially and temporally regulated during spermatogenesis being most highly expressed in the haploid round spermatid stage. Active genes gain H2A.B where it directly interacts with polymerase II and RNA processing factors within splicing speckles. However, the importance of H2A.B for gene expression and fertility are unknown.
resultsHere, we report the first mouse knockout of this histone variant and its effects on fertility, nuclear organization, and gene expression. In view of the controversy related to the generation of off-target mutations by gene editing approaches, we test the specificity of TALENs by disrupting the H2A.B multi-copy gene family using only one pair of TALENs. We show that TALENs do display a high level of specificity since no off-target mutations are detected by bioinformatics analyses of exome sequences obtained from three consecutive generations of knockout mice and by Sanger DNA sequencing. Male H2A.B.3 knockout mice are subfertile and display an increase in the proportion of abnormal sperm and clogged seminiferous tubules. Significantly, a loss of proper RNA Pol II targeting to distinct transcription-splicing territories and changes to pre-mRNA splicing are observed.
conclusionWe have produced the first H2A.B knockout mouse using the TALEN approach.
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