environmentally induced foregut remodeling by pha-4/foxa and daf-12/nhr
DESCRIPTION
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. Pharyngeal devleopment depends on pha-4. - PowerPoint PPT PresentationTRANSCRIPT
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
Ph-M (muscle) Ph-MC(marginal cells) Ph-MMC(combine above) Ph-G(glands) Epi (epithelial)
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
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
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?
Down regulation observed in Dauer animals
Food restoration returned animals to growth phase
Daf12 effect repression or loss of activation
PHA-4 binding sites not required for repression