A histone H3.3K36M mutation in mice causes an imbalance of histonemodifications and defects in chondrocyte differentiation.

Abe, Shusaku and Nagatomo, Hiroaki and Sasaki, Hiroyuki and Ishiuchi,Takashi

Histone lysine-to-methionine (K-to-M) mutations have been identified as driver mutations in human cancers. Interestingly, these 'oncohistone' mutations inhibit the activity of histone methyltransferases. Therefore, they can potentially be used as versatile tools to investigate the roles of histone modifications. In this study, we generated a genetically engineered mouse line in which an H3.3K36M mutation could be induced in the endogenous gene. Since H3.3K36M has been identified as a causative mutation of human chondroblastoma, we induced this mutation in the chondrocyte lineage in mouse embryonic limbs. We found that H3.3K36M causes a global reduction in H3K36me2 and defects in chondrocyte differentiation. Importantly, the reduction of H3K36me2 was accompanied by a collapse of normal H3K27me3 distribution. Furthermore, the changes in H3K27me3, especially the loss of H3K27me3 at gene regulatory elements, were associated with the mis-regulated expression of a set of genes important for limb development, including HoxA cluster genes. Thus, through the induction of the H3.3K36M mutation, we reveal the importance of maintaining the balance between H3K36me2 and H3K27me3 during chondrocyte differentiation and limb development.


Share this article

November, 2020


Products used in this publication

  • ChIP-seq Grade
    H3K27me3 Antibody
  • Antibody ChIP icon
    H3K36me2 Antibody


  • ASH 2023
    San Diego, California, USA
    Dec 9-Dec 12, 2023
 See all events


 See all news

The European Regional Development Fund and Wallonia are investing in your future.

Extension of industrial buildings and new laboratories.

       Site map   |   Contact us   |   Conditions of sales   |   Conditions of purchase   |   Privacy policy   |   Diagenode Diagnostics