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| Status |
Public on Nov 01, 2020 |
| Title |
A histone H3.3K36M mutation in mice causes imbalance of histone modifications and defects in chondrocyte differentiation [ChIP-seq] |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
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.
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| Overall design |
ChIP-seq for H3K36me2, H3K36me3, and H3K27me3 were performed in mouse E14.5 tibial midshafts. mRNA-seq was performed in mouse E14.5 tibial midshafts and ends.
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| Contributor(s) |
Ishiuchi T, Abe S |
| Citation(s) |
33135541 |
| Submission date |
May 11, 2020 |
| Last update date |
Feb 08, 2021 |
| Contact name |
Takashi Ishiuchi |
| Organization name |
Kyushu University
|
| Department |
Medical Institute of Bioregulation
|
| Lab |
Epigenetics and Development
|
| Street address |
3-1-1 Maidashi, Higashi-ku
|
| City |
Fukuoka |
| ZIP/Postal code |
812-8582 |
| Country |
Japan |
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| Platforms (1) |
| GPL18480 |
Illumina HiSeq 1500 (Mus musculus) |
|
| Samples (16)
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| This SubSeries is part of SuperSeries: |
| GSE150353 |
A histone H3.3K36M mutation in mice causes imbalance of histone modifications and defects in chondrocyte differentiation |
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| Relations |
| BioProject |
PRJNA631842 |
| SRA |
SRP261200 |
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