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| Status |
Public on Feb 17, 2017 |
| Title |
TFAP2A ChIP-seq in mouse immortalized melanocytes |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Damage to the gene regulatory network governing terminal differentiation of melanocytes leads to pigmentation phenotypes and increases the risk for melanoma. Microphthalmia-associated transcription factor (MITF) directly activates expression of melanocyte differentiation effectors, and levels of MITF have been proposed to govern the melanoma phenotype. Mutations in the gene encoding Transcription Factor Activator Protein 2 alpha (TFAP2A) cause reduced pigmentation in model organisms and premature hair graying in humans, and TFAP2A expression tends to be lower in advanced melanoma tumors than in benign nevi. However, the transcriptional targets of TFAP2A in melanocytes, and the epistatic relationship of TFAP2A and MITF, have been unclear. Using microarray-based analysis of zebrafish tfap2a mutant embryos, we generated a profile of genes whose expression is Tfap2a-dependent. We conducted anti-TFAP2A chromatin immunoprecipitation followed by next-generation sequencing (ChIP-seq) in immortalized mouse melanocytes and human primary melanocytes, and discovered that TFAP2A peaks are present near the promoters of Tfap2a-dependent genes expressed in melanocytes, and also at the majority of enhancers active in melanocytes. Comparison of TFAP2A ChIP-seq data to published MITF ChIP-seq data showed that the set of genes with promoters bound by both MITF and TFAP2A is enriched for the gene ontology term “pigment cell differentiation.” Deletion analysis of one such co-bound promoter, for Transient Receptor Potential Melastatin-like 1(TRPM1), confirmed that its expression depends on the presence of MITF binding sites as previously shown, but also depends on the presence of TFAP2A binding sites. Finally, we find that mitfa and tfap2a interact genetically in zebrafish. Collectively, these results show that TFAP2A, operating in parallel with MITF, directly regulates effectors of terminal differentiation in melanocytes and melanoma.
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| Overall design |
TFAP2A ChIP-seq was conducted in a mouse immortalized melanocyte cell line (melan-a cells). TFAP2A enriched chromatin was compared to an input control.
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| Web link |
http://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1006636
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| Contributor(s) |
Loftus SK, Pavan WJ, Cornell RA |
| Citation(s) |
28249010 |
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| Submission date |
Sep 11, 2015 |
| Last update date |
May 15, 2019 |
| Contact name |
Stacie Loftus |
| E-mail(s) |
sloftus@mail.nih.gov
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| Phone |
301-594-1752
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| Organization name |
National Human Genome Research Institute
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| Street address |
49 Convent Dr
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| City |
Bethesda |
| ZIP/Postal code |
20892 |
| Country |
USA |
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| Platforms (1) |
| GPL11002 |
Illumina Genome Analyzer IIx (Mus musculus) |
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| Samples (3) |
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| Relations |
| BioProject |
PRJNA295400 |
| SRA |
SRP063617 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE72953_RAW.tar |
1.3 Gb |
(http)(custom) |
TAR (of BIGWIG, NARROWPEAK) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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