Environmentally induced foregut remodeling by PHA-4/FoxA and DaF- 12/NHR 1Wanyuan Ao, 1Jeb Gaudet, 2W. james Kent, 1Srikanth Muttumu, 1Susan E. Mango 1Huntsman cancer institute, University of Utah 2Genome bioinformatics Group, University of California
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Environmentally induced foregut remodeling by PHA-4/FoxA and DaF-12/NHR 1Wanyuan Ao, 1Jeb Gaudet, 2W. james Kent, 1Srikanth Muttumu, 1Susan E. Mango 1Huntsman.
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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
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?
Combinatorial regulation
Multiple TF’s working towards common or different goals to attain the outcome necessary for tissue differentiation and activity.
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
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
Uncharacterized genes used to validate assignments
Five displayed enhancer activity
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
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.
M-2 not effected byT-box binding proteins
Yeast one hybrid used to discover transcription factor which binds M-2
Daf-12 is determined a regulatory element in vivo
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• 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?