ESE-1, an Enterocyte-specific Ets Transcription Factor, Regulates MIP-3α Gene Expression in Caco-2 Human Colonic Epithelial Cells

Kwon, John H.; Keates, Sarah; Simeonidis, Simos; Grall, Franck; Libermann, Towia A.; Keates, Andrew C.

doi:10.1074/jbc.m208241200

Cited by 57 publications

(58 citation statements)

References 66 publications

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“…5 and data not shown). Binding sites for IRF-3 and classical NF-B dimers, such as RelA:p50 implicated in the induction of inflammatory chemokines, or binding sites for nonclassical NF-B dimers RelB:p52, implicated in driving homeostatic chemokine gene expression (7,(37)(38)(39)(40)(41)(42)(43)(44)(45), were not detected within a region covering Ϫ2000 to ϩ25 bp of the CCL25 promoter, supporting the notion that these factors are not directly involved in the regulation of CCL25 expression.…”

Section: The Ccl25 Promoter Contains Putative Binding Sites For CDX Tmentioning

confidence: 65%

“…Promoter analysis using MatInspector predicted a binding site for this repressor (CLOX/CDP) within the CCL25 promoter. Similarly, regulation of the chemokine CCL20 in colonic epithelial cells is obtained through the combined effects of NF-B, Sp1, and ESE-1, an enterocyte specific transcription factor (42). In this regard, the CCL25 promoter contains putative binding sites for Krueppel-like factors, a family of transcription factors implicated in driving expression of intestinal genes (58), indicating that CCL25 may belong to an intestine restricted gene battery.…”

Section: Discussionmentioning

confidence: 99%

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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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Section: The Ccl25 Promoter Contains Putative Binding Sites For CDX Tmentioning

confidence: 65%

Section: Discussionmentioning

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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“…To determine whether the interaction of IFI16 with NF-kB may also be responsible for the induction of other genes within the IFI16 secretome, functional analysis of the CCL20 gene promoter was performed. To do this, transient transfection assays were performed using either one of the two human CCL20 promoter-luciferase constructs: pCCL20 c/EBPmut, containing the full-length human CCL20 promoter bearing the mutated c/EBP site; and the pCCL20 NF-kBmut, containing the full-length CCL20 promoter bearing the mutated NF-kB site [14]. As shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

The interferon‐inducible gene IFI16 secretome of endothelial cells drives the early steps of the inflammatory response

et al. 2010

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The IFN-inducible human IFI16 gene is highly expressed in endothelial cells as well as epithelial and hematopoietic tissues. Previous gene array analysis of human umbilical vein endothelial cells overexpressing IFI16 has revealed an increased expression of genes involved in inflammation and apoptosis. In this study, protein array analysis of the IFI16 secretome showed an increased production of chemokines, cytokines and adhesion molecules responsible for leukocyte chemotaxis. Functional analysis of the promoter for CCL20, the chemokine responsible for leukocyte recruitment in the early steps of inflammation, by site-specific mutation demonstrated that NF-jB is the main mediator of CCL20 induction at the transcriptional level. Finally, both Langerhans DC and B-lymphocyte migration triggered by supernatants from IFI16-overexpressing endothelial cells was partially inhibited by Ab inactivating CCL4, CCL5 and CCL20 chemokines. Altogether, these results demonstrate that the IFI16 gene, through its secretome, regulates proinflammatory activity of endothelial cells, thus corroborating its role in the early steps of inflammation.

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“…34 In human colonic epithelial cells, ESE-1 has also been shown to regulate gene expression of the proinflammatory cytokine, macrophage inflammatory protein-3a (MIP-3a). 39 Another group has previously reported that CR6-interacting factor 1 (Crif1) plays an essential role in Elf3-mediated intestinal development by functioning as a transcriptional co-activator of Elf3 during terminal differentiation of the 25,30 Mouse bronchiolar airway epithelium 42 Mouse embryonal carcinoma cell line (F9) 33,35,37 Human embryonic kidney cell line (HEK 293T) 33,35,37 Human hepatoblastoma cell line (HepG2) 31 Human gastric cancer cell line (SNU-620) 31 Human colon cancer cell line (RKO) 34 Human breast cancer cell lines (SK-BR3, Hs578t) 31,32 Human cervical cancer cell line (HeLa 229) 31,33 Macrophage inflammatory protein-3a (MIP-3a)m Human colonic epithelial cell line (Caco-2) 39 Small proline-rich protein 1B (SPRR1B)m Primary human tracheobronchial epithelial cells 41 Human bronchial epithelial cell line (BEAS-2B) 41 Human lung adenocarcinoma epithelial cell line (NCI-H441) 41 Epithelium-specific ETS transcription factor-3 (ESE-3)m Human bronchial epithelial cell line (BEAS-2B) 44 Human lung carcinoma cell line (A549) 44 Interleukin-6 (IL-6)m Mouse lung tissue 44 Primary mouse airway epithelial cells 47 Primary mouse bone marrow-derived dendritic cells 47 Human bronchial epithelial cell line (BEAS-2B) 47 Interleukin-12 (IL-12)m Primary mouse bone marrow-derived dendritic cells 47 Lysozyme (LYZ)m Primary human bronchial airway epithelial cells 46 Human lung carcinoma cell line (A549) 46 Human lung mucoepidermoid carcinoma-derived cell line (NCI-H292) 46 Human lung adenocarcinoma epithelial cell line (NCI-H441) …”

Section: Ese-1 In Regulating Epithelial Cell Differentiation During Imentioning

confidence: 99%

Multiple roles of the epithelium-specific ETS transcription factor, ESE-1, in development and disease

Oliver

Kushwah

2012

Laboratory Investigation

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The E26 transformation-specific (ETS) family of transcription factors comprises of 27 and 26 members in humans and mice, respectively, which are known to regulate many different biological processes, including cell proliferation, cell differentiation, embryonic development, neoplasia, hematopoiesis, angiogenesis, and inflammation. The epitheliumspecific ETS transcription factor-1 (ESE-1) is a physiologically important ETS transcription factor, which has been shown to play a role in the pathogenesis of various diseases, and was originally characterized as having an epithelial-restricted expression pattern, thus placing it within the epithelium-specific ETS subfamily. Despite a large body of published work on ETS biology, much remains to be learned about the precise functions of ESE-1 and other epithelium-specific ETS factors in regulating diverse disease processes. Clues as to the specific function of ESE-1 in the setting of various diseases can be obtained from studies aimed at examining the expression of putative target genes regulated by ESE-1. Thus, this review will focus primarily on the various roles of ESE-1 in different pathophysiological processes, including regulation of epithelial cell differentiation during both intestinal development and lung regeneration; regulation of dendritic cell-driven T-cell differentiation during allergic airway inflammation; regulation of mammary gland development and breast cancer; and regulation of the effects of inflammatory stimuli within the setting of synovial joint and vascular inflammation. Understanding the exact mechanisms by which ESE-1 regulates these processes can have important implications for the treatment of a wide range of diseases. KEYWORDS: cancer; development; epithelial cell differentiation; ESE-1; ETS transcription factor; inflammation; regeneration The E26 transformation-specific (ETS) family of transcription factors is characterized by a highly conserved 84-aminoacid DNA-binding domain, known as the ETS domain. 1 Because the first member of the ETS family, the v-ets oncogene, was originally discovered as part of a fusion protein with gag and myb expressed by the E26 avian erythroblastosis-transforming retrovirus and its DNA-binding domain is E26 transformation-specific, this 84-amino-acid DNA-binding domain was named the ETS domain. 1 The ETS domain is usually located within the carboxyl-terminal region of the protein as a winged helix-turn-helix structural motif and mediates binding to sites of purine-rich DNA, commonly containing a core consensus sequence of GGAA/T, within the promoter and enhancer regions of target genes. 2,3 Many ETS transcription factors also contain a pointed domain, which is located within the amino-terminal region and is involved in protein-protein interactions. 2 Approximately 30 members of the ETS transcription factor family have been identified in mammals (ie 27 in humans and 26 in mice), 4 and have been shown to play crucial roles in the regulation of many physiological and pathological processes, such as embryonic develo...

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ESE-1, an Enterocyte-specific Ets Transcription Factor, Regulates MIP-3α Gene Expression in Caco-2 Human Colonic Epithelial Cells

Cited by 57 publications

References 66 publications

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

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

The interferon‐inducible gene IFI16 secretome of endothelial cells drives the early steps of the inflammatory response

Multiple roles of the epithelium-specific ETS transcription factor, ESE-1, in development and disease

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