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Related Concept Videos

Histone Variants at the Centromere02:30

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Histone variants are the histone proteins with structural and sequence variations. These variants may be regarded as “mutant” forms that replace their canonical histone counterparts in the nucleosomes. Specific post-translational modifications on the histone variants enable further chromatin complexity and regulate tissue-specific gene expression. The most common histone variants are from histone H2A, H2B, and linker histone H1 families. However, several variants of histone H3...
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Chromatin modification alters gene expression; therefore, scientists can add histone-modifying enzymes, histone variants, and chromatin remodeling complexes to somatic cells to aid reprogramming into pluripotent stem (iPS) cells.
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The histone proteins have a flexible N-terminal tail extending out from the nucleosome. These histone tails are often subjected to post-translational modifications such as acetylation, methylation, phosphorylation, and ubiquitination. Particular combinations of these modifications form “histone codes” that influence the chromatin folding and tissue-specific gene expression.
Acetylation
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Related Experiment Video

Updated: Jan 9, 2026

A Seminiferous Tubule Squash Technique for the Cytological Analysis of Spermatogenesis Using the Mouse Model
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IGF2BP3 recognizes m6A to regulate histone-to-protamine replacement during mouse sperm development.

Dazhuang Wang1, Zhenyi Huang1, Yichun Zhou1

  • 1Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, Department of Developmental Biology, School of Basic Medical Sciences, Southern Medical University, 510515, Guangzhou, P. R. China.

The EMBO Journal
|December 5, 2025
PubMed
Summary

The m6A reader protein IGF2BP3 is crucial for male fertility. Its absence causes spermatogenesis defects by increasing translation of histone-to-protamine replacement factors, leading to infertility.

Keywords:
IGF2BP3Protamine ReplacementSpermiogenesisTranslation Inhibitionm6A Reader

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Area of Science:

  • Reproductive Biology
  • Molecular Biology
  • Epigenetics

Background:

  • Spermatid development relies on RNA metabolism, including N6-methyladenosine (m6A) modifications.
  • The roles of specific m6A reader proteins in post-meiotic spermiogenesis are not well understood.

Purpose of the Study:

  • To investigate the function of the m6A reader protein IGF2BP3 in post-meiotic spermatid development.
  • To elucidate the regulatory mechanisms by which IGF2BP3 controls sperm development.

Main Methods:

  • Utilized genetic ablation (knockout) of Igf2bp3 in mice.
  • Investigated RNA translation and protein interactions.
  • Employed siRNA to target specific genes (Dot1l, Hdac11) for rescue experiments.

Main Results:

  • Igf2bp3 deficiency caused spermatogenesis defects and male sub-fertility/infertility.
  • Loss of IGF2BP3 led to increased translation of target RNAs (Dot1l, Hdac11) involved in histone-to-protamine replacement.
  • IGF2BP3 translationally represses targets via m6A binding and YBX2 interaction.
  • Knockout phenotypes were rescued by targeting Dot1l and Hdac11.

Conclusions:

  • IGF2BP3 is essential for regulating protein biosynthesis during spermiogenesis, specifically in histone-to-protamine replacement.
  • This study clarifies the role of m6A RNA modification in male fertility and sperm development.