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| Status |
Public on Feb 29, 2016 |
| Title |
AP-1 family members act at DNA targets in conjunction with Sox9 to promote chondrocyte hypertrophy |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
Expression profiling by high throughput sequencing
|
| Summary |
A comprehensive analysis of Sox9 binding profiles in developing chondrocytes identified marked enrichment of an AP-1-like motif (Ohba et al. 2015). Here, we have explored the functional interplay between Sox9 and AP-1 in mammalian chondrocyte development. Among AP-1 family members, Jun and Fosl2 were highly expressed within prehypertrophic and early hypertrophic chondrocytes. Chromatin immunoprecipitation followed by DNA sequencing (ChIP-seq) showed a striking overlap in Jun- and Sox9-bound regions throughout the chondrocyte genome, a reflection of direct binding of each factor to target motifs in shared enhancers, and physical interactions of AP-1 with Sox9. In vitro expression analysis indicates that direct co-binding of Sox9 and AP-1 at target motifs enhanced target gene expression, while protein-protein interactions suppressed AP-1- and Sox9-driven transcription. Analysis of prehypertrophic chondrocyte removal of Sox9 demonstrated Sox9 was essential for hypertrophic chondrocyte development, while in vitro and ex vivo analyses showed AP-1 promotes chondrocyte hypertrophy. Sox9 and Jun co-bound and co-activated a Col10a1 enhancer in Sox9 and AP-1 motif-dependent manners consistent with their combined action promoting hypertrophic gene expression. Together, the data support a model where AP-1-family members promote Sox9-action in the transition of chondrocytes to a terminal hypertrophic program.
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| Overall design |
Intersection of ChIP-seq data from Sox9 and AP-1 factor Jun, RNA-seq data from developing rib chondrocytes and Col10a1mCherry positive hypertrophic chondrocytes in neonatal mice to uncover regulation of Sox9 by AP-1 factors during chondrocyte hypertrophy.
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| |
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| Contributor(s) |
He X, Ohba S, Hojo H, McMahon AP |
| Citation(s) |
27471255 |
| |
| Submission date |
Sep 23, 2015 |
| Last update date |
May 15, 2019 |
| Contact name |
Xinjun He |
| E-mail(s) |
[email protected]
|
| Phone |
323-442-8077
|
| Organization name |
University of Southern California
|
| Department |
BROAD CIRM Center
|
| Street address |
1425 San Pablo St
|
| City |
Los Angeles |
| State/province |
CA |
| ZIP/Postal code |
90033 |
| Country |
USA |
| |
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| Platforms (2) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
|
| Samples (6)
|
| GSM1975840 |
Rib_Chondrocyte_Col10a1mCherry_Sorted-2_RNA-seq |
| GSM1975841 |
Rib_Chondrocyte_Col10a1mCherry_Sorted-3_RNA-seq |
| GSM1975842 |
Rib_Chondrocyte_Col10a1mCherry_Sorted-4_RNA-seq |
|
| Relations |
| BioProject |
PRJNA296816 |
| SRA |
SRP064134 |
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