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Environmentally induced foregut remodeling by PHA-4/FoxA and DaF-12/NHR

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.

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Environmentally induced foregut remodeling by PHA-4/FoxA and DaF-12/NHR

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  1. 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

  2. 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?

  3. Combinatorial regulation Multiple TF’s working towards common or different goals to attain the outcome necessary for tissue differentiation and activity.

  4. 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)

  5. 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

  6. Uncharacterized genes used to validate assignments

  7. Five displayed enhancer activity

  8. 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

  9. 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.

  10. M-2 not effected byT-box binding proteins

  11. Yeast one hybrid used to discover transcription factor which binds M-2

  12. Daf-12 is determined a regulatory element in vivo

  13. 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?

  14. Down regulation observed in Dauer animals

  15. Food restoration returned animals to growth phase

  16. Daf12 effect repression or loss of activation

  17. PHA-4 binding sites not required for repression

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