Field of study:
Mechanisms of transcriptional
regulation by cell signaling pathways during development.
Research focus:
A few highly conserved cell signaling pathways
(e.g. Hedgehog, Wnt, Notch) control the vast majority of cell fate
decisions during animal development. These pathways regulate the
activity of transcription factors, which in turn regulate pathway
target genes by binding to regions of genomic DNA called enhancers.
Enhancers generally contain binding sites for several transcription
factors, each of which either activates or represses gene expression.
However, “synthetic” versions of well-characterized
enhancers (i.e., combinations of the known transcription factor
binding sites) nearly always fail to drive gene expression in vivo.
Therefore, it seems that we don’t yet know all of the component
parts of the enhancer, or its basic structure. These experiments
raise the possibility that unidentified DNA-binding proteins, which
may be functionally distinct from transcription factors, are essential
for gene activation in higher eukaryotes. Are such proteins “enhancer
competence factors”? How do these proteins interact with signal-regulated
transcription factors to activate transcription?
Research goal:
To define the component parts and molecular
organization of the signal-regulated enhancer, by (1) identifying
novel DNA-binding proteins required for enhancer function and (2)
discovering the rules by which enhancer-binding proteins interact
to promote (or inhibit) target gene activation in vivo. Using the
Drosophila model system, my lab will employ biochemical, genetic,
bioinformatic, evolutionary, and transgenic approaches to the study
of these problems.
Recent Publications:
- Barolo, S., Castro, B., and Posakony, J.W. (2004.) New Drosophila transgenic reporters: Insulated P element vectors expressing fast-maturing RFP. BioTechniques 36: 436-449. [cover image]
- Barolo, S. and Posakony, J.W. (2002). Three
habits of highly effective signaling pathways: Principles of transcriptional
control by developmental cell signaling.
Genes & Development 16(10):1167-1181.
- Barolo, S., Stone, T., Bang, A., and Posakony,
J.W. (2002). Hairless acts as an adaptor which recruits the corepressors
Groucho and CtBP to Suppressor of Hairless.
Genes & Development 16:1964–1976.
- Barolo, S., Walker, R.G., Polyanovsky, A.,
Freschi, G., Keil, T., and Posakony, J.W. (2000). A Notch-independent
activity of Suppressor of Hairless is required for normal mechanoreceptor
physiology.
Cell 103: 957-969.
- Barolo, S., Carver, L., and Posakony, J.W.
(2000). GFP and ß-galactosidase transformation vectors for
promoter/enhancer analysis in Drosophila.
BioTechniques 29: 726-732.
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