Mesenchymal Transcription Factor Fkh6 Is Essential for the Development and Differentiation of Parietal Cells

Fukamachi, Hiroshi; Fukuda, Katsuyuki; Suzuki, Munekazu; Furumoto, Takaaki; Ichinose, Masakazu; Shimizu, Satoshi; Tsuchiya, Shizuko; Horie, Shunji; Suzuki, Yasuo; Saitō, Yasushi; Watanabe, Kazuo; Taniguchi, Masaru; Koseki, Haruhiko

doi:10.1006/bbrc.2001.4247

Cited by 15 publications

(10 citation statements)

References 25 publications

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“…Gene targeting of Zfp277 was performed as described previously [58]. Briefly, a gene-targeting vector was generated using a BAC clone containing the Zfp277 gene obtained from a mouse 129/Sv BAC library (Invitrogen).…”

Section: Methodsmentioning

confidence: 99%

A Novel Zinc Finger Protein Zfp277 Mediates Transcriptional Repression of the Ink4a/Arf Locus through Polycomb Repressive Complex 1

et al. 2010

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BackgroundPolycomb group (PcG) proteins play a crucial role in cellular senescence as key transcriptional regulators of the Ink4a/Arf tumor suppressor gene locus. However, how PcG complexes target and contribute to stable gene silencing of the Ink4a/Arf locus remains little understood.Methodology/Principal FindingsWe examined the function of Zinc finger domain-containing protein 277 (Zfp277), a novel zinc finger protein that interacts with the PcG protein Bmi1. Zfp277 binds to the Ink4a/Arf locus in a Bmi1-independent manner and interacts with polycomb repressor complex (PRC) 1 through direct interaction with Bmi1. Loss of Zfp277 in mouse embryonic fibroblasts (MEFs) caused dissociation of PcG proteins from the Ink4a/Arf locus, resulting in premature senescence associated with derepressed p16Ink4a and p19Arf expression. Levels of both Zfp277 and PcG proteins inversely correlated with those of reactive oxygen species (ROS) in senescing MEFs, but the treatment of Zfp277 −/− MEFs with an antioxidant restored the binding of PRC2 but not PRC1 to the Ink4a/Arf locus. Notably, forced expression of Bmi1 in Zfp277 −/− MEFs did not restore the binding of Bmi1 to the Ink4a/Arf locus and failed to bypass cellular senescence. A Zfp277 mutant that could not bind Bmi1 did not rescue Zfp277 −/− MEFs from premature senescence.Conclusions/SignificanceOur findings implicate Zfp277 in the transcriptional regulation of the Ink4a/Arf locus and suggest that the interaction of Zfp277 with Bmi1 is essential for the recruitment of PRC1 to the Ink4a/Arf locus. Our findings also highlight dynamic regulation of both Zfp277 and PcG proteins by the oxidative stress pathways.

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Section: Methodsmentioning

confidence: 99%

A Novel Zinc Finger Protein Zfp277 Mediates Transcriptional Repression of the Ink4a/Arf Locus through Polycomb Repressive Complex 1

et al. 2010

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“…Foxl1 Ϫ/Ϫ mice were backcrossed onto a BALB/c background 10 times (7). The morning of the appearance of a vaginal plug was considered to be 0.5 day postcoitus (dpc).…”

Section: Methodsmentioning

confidence: 99%

“…We and others have recently reported that Foxl1 Ϫ/Ϫ mice demonstrate multiple pathological symptoms, including impaired acid secretion by gastric parietal cells, defect in small intestinal uptake of D-glucose, and abnormal formation of gut-associated lymphoid follicles (7,8,18,19,27). These observations raise the possibility that Foxl1 may function as a multifunctional regulator in the context of the mesenchymalepithelial interaction.…”

mentioning

confidence: 88%

Foxl1-deficient mice exhibit aberrant epithelial cell positioning resulting from dysregulated EphB/EphrinB expression in the small intestine

Takano-Maruyama¹,

Hase²,

Fukamachi

et al. 2006

American Journal of Physiology-Gastrointestinal and Liver Physi

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The winged helix transcription factor Foxl1, expressed in the gut mesenchyme, regulates epithelial cell proliferation and differentiation through the Wnt/beta-catenin pathway. To better understand the role of Foxl1 in epithelial morphogenesis, we examined the tissue structure and positioning of epithelial cells in the small intestine of Foxl1-deficient mice. The small intestine of Foxl1-deficient mice manifested aberrant crypt structure, including widely distributed Paneth cells, which coincided with the ectopic and increased expression of EphB2 and EphB3, which are key regulators of epithelial cell positioning. Furthermore, real-time quantitative PCR indicated that a subset of Wnt family genes was highly expressed in the gut mesenchyme of Foxl1-deficient mice compared with that of wild-type mice. Such an increase in Wnt expression was remarkable in the mesenchyme, where the aberrant Paneth cell positioning was observed by in situ hybridization. Foxl1 plays an important role in the maintenance of crypt architecture and epithelial cell positioning through the mesenchymal-epithelial interaction in the small intestine. This interaction is essential for the normal regulation of the Wnt/beta-catenin pathway and the subsequent EphB/EphrinB expression.

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“…60 Loss of FoxL1 severely abrogates basal and histamine-stimulated gastric acid secretion, without affecting the cellular canaliculi architecture. 59 A related transcription factor, FoxF1, is co-expressed with FoxL1 in the developing gut mesoderm, and both are direct targets of Hedgehog signaling through Gli2 and Gli3. 61 In the adult, FoxL1 indirectly targets Wnt/b-catenin signaling by upregulating extracellular matrix heparin sulfate proteoglycans, which in turn increase the local concentration of Wnt ligand for binding to Frizzled receptors that are expressed in the epithelium.…”

Section: F Forkhead-box (Fox) Familymentioning

confidence: 99%

The Gastric Mucosa

Khurana

Mills

2010

Progress in Molecular Biology and Translational Science

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Mesenchymal Transcription Factor Fkh6 Is Essential for the Development and Differentiation of Parietal Cells

Cited by 15 publications

References 25 publications

A Novel Zinc Finger Protein Zfp277 Mediates Transcriptional Repression of the Ink4a/Arf Locus through Polycomb Repressive Complex 1

A Novel Zinc Finger Protein Zfp277 Mediates Transcriptional Repression of the Ink4a/Arf Locus through Polycomb Repressive Complex 1

Foxl1-deficient mice exhibit aberrant epithelial cell positioning resulting from dysregulated EphB/EphrinB expression in the small intestine

The Gastric Mucosa

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