Environmentally induced foregut remodeling by PHA-4/FoxA and DaF-12/NHR
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Environmentally induced foregut remodeling by PHA-4/FoxA and
DaF-12/NHR1Wanyuan Ao, 1Jeb Gaudet, 2W. james Kent, 1Srikanth
Muttumu, 1Susan E. Mango1Huntsman cancer institute, University of Utah
2Genome bioinformatics Group, University of California
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Pharyngeal devleopment depends on pha-4
Embryos that lack pha-4 fail to generate pharyngeal cells.
Many and possibly all genes expressed in the pharynx(at all stages) require pha-4 for activation
What causes variation in expression?
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Combinatorial regulation
Multiple TF’s working towards common or different goals to attain the outcome necessary for tissue differentiation and activity.
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1 The Aproach
Expression profiles for 339 pharyngeal genes Identified by microarray analysis
Five clusters of genes with shared expression profiles were determined for use with topographical expression maps
Ph-M (muscle) Ph-MC(marginal cells) Ph-MMC(combine above) Ph-G(glands) Epi (epithelial)
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2
Algorithm created to Identify potential cis-regulatory elements
Uses set of 194 randomly selected genes not expressed in pharynx as a negative control
Seven candidate elements determined
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Uncharacterized genes used to validate assignments
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Five displayed enhancer activity
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Proposed mechanism for expression
PHA-4 sites contribute to organ-wide activation throughout pharynx and additional elements impart positional (29-4) cell type (M-2,12-1,12-5) information
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3 the M-2 motif
Highly selective for pharyngeal muscle.
Four genes selected which carried consensus in both C elegans and C briggsae and were expressed in pharyngeal muscle.
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M-2 not effected byT-box binding proteins
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Yeast one hybrid used to discover transcription factor which binds M-2
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Daf-12 is determined a regulatory element in vivo
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4
• Choice of Growth phase and Dauer development depends on insulin, TGF-B and heterotrimeric guanine nucleotide-binding protein coupled receptor signaling pathways.
• DAF-12 is affected, what effect does it have on these biological functions?
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Down regulation observed in Dauer animals
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Food restoration returned animals to growth phase
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Daf12 effect repression or loss of activation
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PHA-4 binding sites not required for repression