Eric Monson and Hannah Seberg will Present their Research on Thursday, 9-17-15

Hannah’s Abstract 

TFAP2A drives melanocyte gene expression in parallel with MITF
H E Seberg1, E Van Otterloo2, S K Loftus3, J P Lambert4, G Bonde2, R Sompallae5, J F Santana1, J R Manak1, A C Gingras4, W J Pavan3, R A Cornell1,2

1 Interdisciplinary Graduate Program in Genetics, University of Iowa
2 Department of Anatomy and Cell Biology, University of Iowa
3 Genetic Disease Research Branch, National Human Genome Research Institute, Bethesda, MD
4 Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada
5 Bioinformatics Division, Iowa Institute of Human Genetics, University of Iowa
Disruption of the transcription factor network governing melanocyte development contributes to the pathogenesis of pigmentation disorders and melanoma. The activity levels of an important member of this network, MITF, have been proposed to control melanoma phenotype. Mid- to high-level MITF activity drives growth and differentiation, while lower levels confer a stem cell-like, invasive quality. Transcription Factor Activator Protein 2 alpha (TFAP2A) expression is reduced in advanced stage melanoma tumors, and mutations in TFAP2A cause pigmentation phenotypes in humans, mice, and zebrafish. Because TFAP2A is widely expressed in the neural crest and skin, its specific role in melanocytes and relationship to MITF has been unclear. To determine the position of TFAP2A in the melanocyte gene regulatory network, we first used microarray analysis of wildtype and tfap2a null zebrafish to profile genes that are downregulated in the absence of TFAP2A. We then conducted anti-TFAP2A ChIP-seq to create a profile of TFAP2A-bound loci in melanocytes. Genes at the intersection of these profiles are likely direct targets of TFAP2A. These include melanin synthesis genes, such as dct, tyrp1, and trpm1, most of which are also thought to be direct targets of MITF. Comparison with published MITF ChIP-seq showed that TFAP2A peaks overlap MITF peaks more often than expected by chance. In reporter assays, deletion of TFAP2A binding sites in a minimal TRPM1 promoter decreased its activity, similar to published results for deletion of MITF binding sites from this element. Furthermore, we found that tfap2a and mitfa interact both physically in vitro and genetically in zebrafish. These results provide evidence that TFAP2A and MITF work in parallel to promote melanocyte differentiation, and show that widely-expressed TFAP2A can directly regulate expression of lineage-specific melanocyte genes. In addition, TFAP2A expression may be able to influence levels of MITF, driving cells toward differentiation and away from an invasive state.

Eric’s Talk Title

Investigating the Human Exome in Suicidal Behavior


Posted on September 17, 2015, in Student Seminar. Bookmark the permalink. Leave a comment.

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