Factors involved in the duodenal expression of the human calbindin-D9k gene

Barley, Natalie F.; Prathalingam, S. Radhika; Zhi, Pang; Legon, S.; Howard, Alison; Walters, Julian R.F.

doi:10.1042/0264-6021:3410491

Cited by 39 publications

(26 citation statements)

References 44 publications

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“…Calbindin also shares the same C/V (38) and developmental (39) patterns of expression as ADA, with minor exceptions. The promoter sequences for each have also been observed to contain sites that can bind PDX-1 in vitro (33,34,37,40). As of yet, no functional studies for either of these sites have been published.…”

Section: Discussionmentioning

confidence: 99%

PDX-1 Is Required for Activation in Vivo from a Duodenum-specific Enhancer

Dusing

Florence

Wiginton

2001

Journal of Biological Chemistry

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The purine metabolic gene adenosine deaminase (ADA) is expressed along a defined spatiotemporal pattern in the developing mammalian small intestine, where high-level expression is limited to the villous epithelium of the duodenum. This activation is observed in rodents as the intestine completes the final maturation resulting in adult crypt-villus structures at 2-3 weeks postpartum. A regulatory module responsible for this pattern of expression has been identified in the second intron of the human ADA gene. Of the multiple duodenal proteins that can interact with this small duodenal enhancer region, the studies contained in this work describe the identification of five of these proteins as the dispersed homeobox protein PDX-1. This transcription factor exhibits a profile of expression in the small intestine similar to that observed for ADA, making it an ideal candidate factor for the duodenum-specific ADA enhancer. Loss of PDX-1 binding, via a PDX-1 mutated enhancer transgenic construction, resulted in complete loss of high-level activation in the duodenum, demonstrating the absolute requirement for this factor in vivo. However, co-transfection experiments suggest that other proteins that bind the enhancer are also required for enhancer function because PDX-1 alone was incapable of significant transactivation.

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Section: Discussionmentioning

confidence: 99%

PDX-1 Is Required for Activation in Vivo from a Duodenum-specific Enhancer

Dusing

Florence

Wiginton

2001

Journal of Biological Chemistry

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“…The presence of putative Cdx-1 and Cdx-2 binding sites within the murine CCL25 promoter was of interest because Cdx-1 and Cdx-2 expression is restricted to the gut epithelium in adult mice (46), and these transcription factors have been implicated in regulating expression of intestinal specific genes (47)(48)(49)(50)(51)(52). Importantly, although freshly isolated small intestinal epithelial cells expressed Cdx-1 and Cdx-2 mRNA (Fig.…”

Section: Interacts With the Predicted Binding Site In The Ccl25 Pmentioning

confidence: 99%

Functional Characterization of the CCL25 Promoter in Small Intestinal Epithelial Cells Suggests a Regulatory Role for Caudal-Related Homeobox (Cdx) Transcription Factors

Ericsson¹,

Kotarsky²,

Svensson³

et al. 2006

The Journal of Immunology

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The chemokine CCL25 is selectively and constitutively expressed in the small intestinal epithelium and plays an important role in mediating lymphocyte recruitment to this site. In this study, we demonstrate that CCL25 expression in murine small intestinal epithelial cells is independent of signaling through the lymphotoxin β receptor and is not enhanced by inflammatory stimuli, pathways involved in driving the expression of most other chemokines. We define a transcriptional start site in the CCL25 gene and a region −141 to −5 proximal of exon 1 that is required for minimal promoter activity in the small intestinal epithelial cell lines, MODE-K and mICc12. These cell lines expressed far less CCL25 mRNA than freshly isolated small intestinal epithelial cells indicating that they are missing important factors driving CCL25 expression. The CCL25 promoter contained putative binding sites for the intestinal epithelial-associated Caudal-related homeobox (Cdx) transcription factors Cdx-1 and Cdx-2, and small intestinal epithelial cells but not MODE-K and mICc12 cells expressed Cdx-1 and Cdx-2. EMSA analysis demonstrated that Cdx proteins were present in nuclear extracts from freshly isolated small intestinal epithelial cells but not in MODE-K or mICcl2 cells, and bound to putative Cdx sites within the CCL25 promoter. Finally, cotransfection of MODE-K cells with Cdx transcription factors significantly increased CCL25 promoter activity as well as endogenous CCL25 mRNA levels. Together these results demonstrate a unique pattern of regulation for CCL25 and suggest a role for Cdx proteins in regulating CCL25 transcription.

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“…This resulted in an altered midgut -hindgut union and agenesis of the cecum. A possible mechanism for the dysmorphogenesis of the proximal colon has been proposed to be due to an inhibition of Cdx-2 actions mediated by PDX-1 transactivation (72).…”

Section: Role Of Pdx-1 In the Developing Pancreasmentioning

confidence: 99%

Pancreas duodenum homeobox-1 regulates pancreas development during embryogenesis and islet cell function in adulthood

Hui

Perfetti²

2002

European Journal of Endocrinology

121

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Pancreas duodenum homeobox-1 (PDX-1) (also known as insulin promoter factor-1, islet/duodenum homeobox-1, somatostatin transactivating factor-1, insulin upstream factor-1 and glucose-sensitive factor) is a transcription factor encoded by a Hox-like homeodomain gene. In humans and other animal species, the embryonic development of the pancreas requires PDX-1, as demonstrated by the identification of an individual with pancreatic agenesis resulting from a mutation that impaired the transcription of a functionally active PDX-1 protein. In adult subjects, PDX-1 is essential for normal pancreatic islet function as suggested by its regulatory action on the expression of a number of pancreatic genes, including insulin, somatostatin, islet amyloid polypeptide, the glucose transporter type 2 and glucokinase. Furthermore, heterozygous mutations of PDX-1 have been linked to a type of autosomal dominant form of diabetes mellitus known as maturity onset diabetes of the young type 4. The dual action of PDX-1, as a differentiation factor during embryogenesis and as a regulator of islet cell physiology in mature islet cells, underscores the unique role of PDX-1 in health and disease of the human endocrine pancreas.

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Factors involved in the duodenal expression of the human calbindin-D9k gene

Cited by 39 publications

References 44 publications

PDX-1 Is Required for Activation in Vivo from a Duodenum-specific Enhancer

PDX-1 Is Required for Activation in Vivo from a Duodenum-specific Enhancer

Functional Characterization of the CCL25 Promoter in Small Intestinal Epithelial Cells Suggests a Regulatory Role for Caudal-Related Homeobox (Cdx) Transcription Factors

Pancreas duodenum homeobox-1 regulates pancreas development during embryogenesis and islet cell function in adulthood

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