PLX304612

GSE150352: A histone H3.3K36M mutation in mice causes imbalance of histone modifications and defects in chondrocyte differentiation [RNA-seq]

• Organsim mouse
• Type RNASEQ
• Target gene
• Project ARCHS4

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, and, therefore, they can potentially be used as versatile tools to investigate the roles of histone modifications. In this study, we created a conditional knock-in mouse line in which a H3.3K36M mutation can be induced in the endogenous H3.3 gene. Since the H3.3K36M mutation 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 global reduction of 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 misregulated expression of a set of genes important for limb development including HoxA cluster genes. Thus, taking advantage of the in vivo induction of H3.3K36M mutation, we reveal the importance of a counterbalance between H3K36me2 and H3K27me3 for chondrocyte differentiation and limb development. SOURCE: Takashi IshiuchiEpigenetics and Development Kyushu University