GEO Logo
   NCBI > GEO > Accession DisplayHelp Not logged in | LoginHelp
GEO help: Mouse over screen elements for information.
Series GSE73372 Query DataSets for GSE73372
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.
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.
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
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
Platforms (2)
GPL13112 Illumina HiSeq 2000 (Mus musculus)
GPL19057 Illumina NextSeq 500 (Mus musculus)
Samples (6)
GSM1891979 Rib_Chondrocyte_Jun_ChIPseq
GSM1891980 Rib_Chondrocyte_Input_Control_ChIPseq
GSM1975839 Rib_Chondrocyte_Col10a1mCherry_Sorted-1_RNA-seq
BioProject PRJNA296816
SRA SRP064134

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE73372_Col10a1mCherry_Sorted_Rib_RNAseq.xlsx 5.6 Mb (ftp)(http) XLSX
GSE73372_chond_cJun_hiseq.2s.FDR1.peaks.bed.gz 878.3 Kb (ftp)(http) BED
SRA Run SelectorHelp
Raw data are available in SRA
Processed data are available on Series record

| NLM | NIH | GEO Help | Disclaimer | Accessibility |
NCBI Home NCBI Search NCBI SiteMap