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1.  Transcriptional Networks in Liver and Intestinal Development 
SUMMARY
The development of the gastrointestinal tract is a complex process that integrates signaling processes with downstream transcriptional responses. Here, we discuss the regionalization of the primitive gut and formation of the intestine and liver. Anterior–posterior position in the primitive gut is important for establishing regions that will become functional organs. Coordination of signaling between the epithelium and mesenchyme and downstream transcriptional responses is required for intestinal development and homeostasis. Liver development uses a complex transcriptional network that controls the establishment of organ domains, cell differentiation, and adult function. Discussion of these transcriptional mechanisms gives us insight into how the primitive gut, composed of simple endodermal cells, develops into multiple diverse cell types that are organized into complex mature organs.
During regionalization of the primitive gut, transcription factors (e.g., Cdx2) and signals from adjacent tissues coordinate gene expression and organ development in both time and space.
doi:10.1101/cshperspect.a008284
PMCID: PMC3428765  PMID: 22952394
2.  Transcriptional Networks in Liver and Intestinal Development 
Development of the gastrointestinal tract is a complex process that uses unique mechanisms and depends heavily on transcriptional activation. Here we discuss the regionalization of the primitive gut and formation of the intestine and liver. Anterior-posterior positioning in the primitive gut is important for establishing regions that will become functional organs. Coordination of transcription factors and signaling factors between the epithelium and mesenchyme is required for intestinal development and homeostasis. Liver development utilizes a complex transcriptional network that is required for organ domain establishment, cell differentiation, and adult function. Discussion of these transcriptional mechanisms gives us insight on how the primitive gut, composed of simple endodermal cells, develops into multiple diverse cell types that are organized into very complex functional mature organs.
doi:10.1101/cshperspect.a008284
PMCID: PMC3428765  PMID: 22952394
3.  Genome-Wide Identification of Binding Sites Defines Distinct Functions for Caenorhabditis elegans PHA-4/FOXA in Development and Environmental Response 
PLoS Genetics  2010;6(2):e1000848.
Transcription factors are key components of regulatory networks that control development, as well as the response to environmental stimuli. We have established an experimental pipeline in Caenorhabditis elegans that permits global identification of the binding sites for transcription factors using chromatin immunoprecipitation and deep sequencing. We describe and validate this strategy, and apply it to the transcription factor PHA-4, which plays critical roles in organ development and other cellular processes. We identified thousands of binding sites for PHA-4 during formation of the embryonic pharynx, and also found a role for this factor during the starvation response. Many binding sites were found to shift dramatically between embryos and starved larvae, from developmentally regulated genes to genes involved in metabolism. These results indicate distinct roles for this regulator in two different biological processes and demonstrate the versatility of transcription factors in mediating diverse biological roles.
Author Summary
The C. elegans transcription factor PHA-4 is a member of the highly conserved FOXA family of transcription factors. These factors act as master regulators of organ development by controlling how genes are turned off and on as tissues are formed. Additionally they regulate genes in response to nutrient levels and control both longevity and survival of the organism. However, the extent to which these factors control similar or distinct gene targets for each of these functions is unknown. For this reason, we have used the technique of chromatin immunoprecipitation followed by deep sequencing (ChIP–Seq), to define the target binding sites of PHA-4 on a genome-wide scale, when it is either functioning as an organ identity regulator or in response to environmental stress. Our data clearly demonstrate distinct sets of biologically relevant target genes for the transcription factor PHA-4 under these two different conditions. Not only have we defined PHA-4 targets, but we established an experimental ChIP–Seq pipeline to facilitate the identification of binding sites for many transcription factors in the future.
doi:10.1371/journal.pgen.1000848
PMCID: PMC2824807  PMID: 20174564
4.  The Target of Rapamycin (TOR) pathway antagonizes pha-4/FoxA to control development and aging 
Current biology : CB  2008;18(18):1355-1364.
SUMMARY
BACKGROUND
FoxA factors are critical regulators of embryonic development and post-embryonic life, but little is know about the upstream pathways that modulate their activity [1]. C. elegans pha-4 encodes a FoxA transcription factor that is required to establish the foregut in embryos, and to control growth and longevity after birth [2–5]. We previously identified the AAA+ ATPase homologue ruvb-1 as a potent suppressor of pha-4 mutations [6].
RESULTS
Here we show that ruvb-1 is a component of the TOR pathway in C. elegans (CeTOR). Both ruvb-1 and let-363/TOR control nucleolar size and promote localization of box C/D snoRNPs to nucleoli, suggesting a role in rRNA maturation. Inactivation of let-363/TOR or ruvb-1 suppresses the lethality associated with reduced pha-4 activity. The CeTOR pathway controls protein homeostasis and also contributes to adult longevity [7, 8]. We find that pha-4 is required to extend adult lifespan in response to reduced CeTOR signaling. Mutations in the predicted CeTOR target rsks-1/S6 kinase or in ife-2/eIF4E also reduce protein biosynthesis and extend lifespan [9–11], but only rsks-1 mutations require pha-4 for adult longevity. In addition, rsks-1, but not ife-2, can suppress the larval lethality associated with pha-4 loss-of-function mutations.
CONCLUSION
The data suggest that pha-4 and the CeTOR pathway antagonize one another to regulate post-embryonic development and adult longevity. We suggest a model in which nutrients promote TOR and S6 kinase signaling, which represses pha-4/FoxA, leading to a shorter lifespan. A similar regulatory hierarchy may function in other animals to modulate metabolism, longevity or disease.
doi:10.1016/j.cub.2008.07.097
PMCID: PMC2615410  PMID: 18804378

Results 1-4 (4)