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Series GSE246805 Query DataSets for GSE246805
Status Public on Jan 01, 2024
Title TFAP2 paralogs regulate midfacial development in part through a conserved ALX genetic pathway [ChIP-seq]
Organism Mus musculus
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary Cranial neural crest development is governed by positional gene regulatory networks (GRNs). Fine-tuning of the GRN components underly facial shape variation, yet how those in the midface are connected and activated remain poorly understood. Here, we show that concerted inactivation of Tfap2a and Tfap2b in the murine neural crest, even during the late migratory phase, results in a midfacial cleft and skeletal abnormalities. Bulk and single-cell RNA-seq profiling reveal that loss of both Tfap2 members dysregulates numerous midface GRN components involved in midface morphogenesis, patterning, and differentiation. Notably, Alx1/3/4 (Alx) transcript levels are reduced, while ChIP-seq analyses suggest TFAP2 directly and positively regulates Alx gene expression. TFAP2 and ALX co-expression in midfacial neural crest cells of both mouse and zebrafish further implies conservation of this regulatory axis across vertebrates. Consistent with this notion in zebrafish, tfap2a mutants present abnormal alx3 expression patterns, Tfap2a binds alx loci, and tfap2a-alx3 genetic interactions are observed. Together, these data demonstrate TFAP2 paralogs regulate vertebrate midfacial development by activating expression of ALX transcription factors.
 
Overall design To investigate the regions of TFAP2 binding, genome wide, E11.5 wild-type craniofacial prominences (including the frontonasal, maxillary, and mandibular prominence) were harvested and subjected to chromatin immunoprecipitation using a TFAP2 antibody (which recognizes TFAP2A, TFAP2B, and TFAP2C). Immunoprecipitated samples along with 'input' were sequenced.
 
Contributor(s) Van Otterloo E, Nguyen T
Citation(s) 38063857
Submission date Nov 01, 2023
Last update date Feb 14, 2024
Contact name Eric Van Otterloo
E-mail(s) eric-vanotterloo@uiowa.edu
Organization name University of Iowa
Street address 801 Newton Rd
City Iowa City
State/province Iowa
ZIP/Postal code 52242
Country USA
 
Platforms (1)
GPL17021 Illumina HiSeq 2500 (Mus musculus)
Samples (2)
GSM7877347 E11.5 FNP/MxP/MdP sonicated and SC184 immunoprecipated chromatin
GSM7877348 E11.5 FNP/MxP/MdP sonicated chromatin, Input
This SubSeries is part of SuperSeries:
GSE246807 TFAP2 paralogs regulate midfacial development in part through a conserved ALX genetic pathway
Relations
BioProject PRJNA1034633

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Supplementary file Size Download File type/resource
GSE246805_sc184_peaks.narrowPeak.gz 240.8 Kb (ftp)(http) NARROWPEAK
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Raw data are available in SRA

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