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PMID: 20714352 Published · epublish English Journal Article Research Support, N.I.H., Extramural

Dynamic chromatin organization during foregut development mediated by the organ selector gene PHA-4/FoxA.

PLoS genetics ·Vol. 6 ·No. 8 ·2010-08-12

Fakhouri TH, Stevenson J, Chisholm AD, Mango SE

Abstract

Central regulators of cell fate, or selector genes, establish the identity of cells by direct regulation of large cohorts of genes. In Caenorhabditis elegans, foregut (or pharynx) identity relies on the FoxA transcription factor PHA-4, which activates different sets of target genes at various times and in diverse cellular environments. An outstanding question is how PHA-4 distinguishes between target genes for appropriate transcriptional control. We have used the Nuclear Spot Assay and GFP reporters to examine PHA-4 interactions with target promoters in living embryos and with single cell resolution. While PHA-4 was found throughout the digestive tract, binding and activation of pharyngeally expressed promoters was restricted to a subset of pharyngeal cells and excluded from the intestine. An RNAi screen of candidate nuclear factors identified emerin (emr-1) as a negative regulator of PHA-4 binding within the pharynx, but emr-1 did not modulate PHA-4 binding in the intestine. Upon promoter association, PHA-4 induced large-scale chromatin de-compaction, which, we hypothesize, may facilitate promoter access and productive transcription. Our results reveal two tiers of PHA-4 regulation. PHA-4 binding is prohibited in intestinal cells, preventing target gene expression in that organ. PHA-4 binding within the pharynx is limited by the nuclear lamina component EMR-1/emerin. The data suggest that association of PHA-4 with its targets is a regulated step that contributes to promoter selectivity during organ formation. We speculate that global re-organization of chromatin architecture upon PHA-4 binding promotes competence of pharyngeal gene transcription and, by extension, foregut development.

MeSH Terms
Animals Caenorhabditis elegans/genetics,growth & development,metabolism Caenorhabditis elegans Proteins/genetics,metabolism Chromatin/genetics,metabolism Digestive System/growth & development,metabolism Gene Expression Regulation, Developmental Organ Specificity Pharynx/growth & development,metabolism Promoter Regions, Genetic Protein Binding Trans-Activators/genetics,metabolism
Chemicals
Caenorhabditis elegans Proteins Chromatin Pha-4 protein, C elegans Trans-Activators
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Fakhouri Tala H I
Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts, United States of America.
Stevenson Jeff
Chisholm Andrew D
Mango Susan E
Conflict of Interest

The authors have declared that no competing interests exist.

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Article Info
Journal
PLoS genetics
Abbr.
PLoS Genet
ISSN
1553-7404
DOI
10.1371/journal.pgen.1001060
Published
2010-08-12
Epub
2010-00-12
Language
English
Region
United States
NLM ID
101239074
PMCID
PMC2920861
Subset
IM
Grants
NIGMS NIH HHS · R01 GM056264-12 · United States
NIGMS NIH HHS · GM054657 · United States
NIGMS NIH HHS · R01 GM056264 · United States
NIGMS NIH HHS · R01 GM056264-13 · United States
NIGMS NIH HHS · R01 GM056264-14 · United States
NIGMS NIH HHS · R01 GM054657 · United States
External Links
PubMed source DOI: 10.1371/journal.pgen.1001060 PMC Full Text View journal details
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