Distinct Functional Interactions of Human Skn-1 Isoforms with Ese-1 during Keratinocyte Terminal Differentiation

Cabral, Adriana; Fischer, David F.; Vermeij, Wilbert P.; Backendorf, Claude

doi:10.1074/jbc.m300508200

Cited by 31 publications

(25 citation statements)

References 36 publications

(52 reference statements)

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“…POU2F3, also known as SKN1a, and FOXQ1 are both transcription factors involved in keratinocyte differentiation and hair shaft development, respectively (Hildesheim et al 2001;Hong et al 2001;Cabral et al 2003;Potter et al 2006). HOX and forkhead transcription factors such as PITX1 and FOXC1 have potential roles as regulators of differentiation (Gage et al 1999;Lehmann et al 2003).…”

Section: Resultsmentioning

confidence: 99%

Control of differentiation in a self-renewing mammalian tissue by the histone demethylase JMJD3

Sen¹,

Webster²,

Barragan³

et al. 2008

Genes Dev.

245

274

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The recent discovery of H3K27me3 demethylases suggests that H3K27me3 may dynamically regulate gene expression, but this potential role in mammalian tissue homeostasis remains uncharacterized. In the epidermis, a tissue that balances stem cell self-renewal with differentiation, H3K27me3, occupies the promoters of many differentiation genes. During calcium-induced differentiation, H3K27me3 was erased at these promoters in concert with loss of PcG protein occupancy and increased binding by the H3K27me3 demethylase, JMJD3. Within epidermal tissue, JMJD3 depletion blocked differentiation, while active JMJD3 dominantly induced it. These results indicate that epigenetic derepression by JMJD3 controls mammalian epidermal differentiation.Supplemental material is available at http://www.genesdev.org.Received March 12, 2008; revised version accepted May 22, 2008. Post-translational modifications of core histone octamer proteins, in the form of phosphorylation, acetylation, ubiquitination, and methylation, have been increasingly appreciated as powerful regulators of gene expression. In Drosophila and mammals, the histone 3 Lys 27 trimethylation mark (H3K27me3) is associated with repression of gene transcription (Lund and van Lohuizen 2004;Barski et al. 2007). Polycomb group proteins (PcG) and their antagonists, the histone demethylases, are epigenetic regulators that control gene expression by modifying the methylation status of H3K27 (Grimaud et al. 2006;Swigut and Wysocka 2007). The PcG protein, Enhancer of Zest Homolog 2 (EZH2), is a histone methyltransferase that can trimethylate H3K27. Two other PcG proteins, Embryonic Ectoderm Development (EED) and Suppressor of Zeste 12 homolog (SUZ12), are necessary for EZH2 to function properly (Pasini et al. 2004). Genome-wide mapping of H3K27me3 marks and PcG target sites in embryonic stem cells has recently suggested a major role for PcG proteins in maintaining H3K27me3 to allow for repression of the differentiated state and promotion of embryonic stem cell self-renewal, with significant enrichment of these proteins on genes encoding homeodomain proteins and other putative differentiation factors Lee et al. 2006). The mechanism reversing such potential repressive influences on differentiation gene expression by H3K27me3 and other histone modifications in somatic tissue is not fully characterized.Among potential mediators of differentiation gene derepression are newly characterized Jumanji C (JmjC) domain-containing proteins, UTX and JMJD3, which are enzymes capable of demethylating promoters marked by H3K27me3. Recently, the H3K27 demethylase activity of UTX and JMJD3 has been shown to act at HOX gene promoters to derepress HOX gene transcription (Agger et al. 2007;Lan et al. 2007;Lee et al. 2007). These histone demethylases were demonstrated in mammalian cells and in live zebrafish to antagonize PcG gene silencing by modifying chromatin to permit gene transcription. During inflammation, bacterial products and cytokines induce JMJD3, which then removes H3K27me3 marks to dere...

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Section: Resultsmentioning

confidence: 99%

Control of differentiation in a self-renewing mammalian tissue by the histone demethylase JMJD3

Sen¹,

Webster²,

Barragan³

et al. 2008

Genes Dev.

245

274

View full text Add to dashboard Cite

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“…59 It has also been demonstrated that Skn-1a, a specific isoform of the transcription factor Skn-1, interacts and functionally cooperates with ESE-1 in transcriptional activation of the SPRR2A promoter in a human keratinocyte cell line. 60 The human keratin 4 gene plays an important role in early differentiation of the esophageal squamous epithelium, and ESE-1 was also reported to suppress basal keratin 4 promoter activity and simultaneously activate the late differentiation linked SPRR2A promoter in both esophageal and cervical cancer epithelial cell lines. 61 Interestingly, both ESE-1 and AP-1 have been shown to regulate cooperatively the expression of another human keratinocyte terminal differentiation marker, SPRR1A, at the proximal promoter region of the gene.…”

Section: Ese-1 In Terminal Differentiation Of the Epidermal Skin Epitmentioning

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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“…For example, gene knockout experiments have revealed that ESE-1 plays a key role in the morphogenesis and terminal differentiation of the murine small intestinal epithelium (32). Additionally, ESE-1 expression is induced upon keratinocyte differentiation (34), and ESE-1 regulates the expression of keratinocyte (5,34), bronchial (38), and retinal (23) epithelial cell gene markers.…”

mentioning

confidence: 99%

“…5A. Further, multiple replicate studies revealed that 100% of GFP-positive transient transfectants (ϳ10 5 …”

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confidence: 99%

The ETS Transcription Factor ESE-1 Transforms MCF-12A Human Mammary Epithelial Cells via a Novel Cytoplasmic Mechanism

Prescott

Koto

Singh³

et al. 2004

Molecular and Cellular Biology

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Several different transcription factors, including estrogen receptor, progesterone receptor, and ETS family members, have been implicated in human breast cancer, indicating that transcription factor-induced alterations in gene expression underlie mammary cell transformation. ESE-1 is an epithelium-specific ETS transcription factor that contains two distinguishing domains, a serine-and aspartic acid-rich (SAR) domain and an AT hook domain. ESE-1 is abundantly expressed in human breast cancer and trans-activates epitheliumspecific gene promoters in transient transfection assays. While it has been presumed that ETS factors transform mammary epithelial cells via their nuclear transcriptional functions, here we show (i) that ESE-1 protein is cytoplasmic in human breast cancer cells; (ii) that stably expressed green fluorescent protein-ESE-1 transforms MCF-12A human mammary epithelial cells; and (iii) that the ESE-1 SAR domain, acting in the cytoplasm, is necessary and sufficient to mediate this transformation. Deletion of transcriptional regulatory or nuclear localization domains does not impair ESE-1-mediated transformation, whereas fusing the simian virus 40 T-antigen nuclear localization signal to various ESE-1 constructs, including the SAR domain alone, inhibits their transforming capacity. Finally, we show that the nuclear localization of ESE-1 protein induces apoptosis in nontransformed mammary epithelial cells via a transcription-dependent mechanism. Together, our studies reveal two distinct ESE-1 functions, apoptosis and transformation, where the ESE-1 transcription activation domain contributes to apoptosis and the SAR domain mediates transformation via a novel nonnuclear, nontranscriptional mechanism. These studies not only describe a unique ETS factor transformation mechanism but also establish a new paradigm for cell transformation in general.ETS transcription factors play crucial roles in several different biological processes, including differentiation and tumorigenesis (36, 41). All ETS factors are characterized by a conserved winged helix-turn-helix DNA binding domain (DBD), the ETS domain, which mediates binding to ets consensus sites in target genes. ETS proteins, which function as activators and/or repressors of gene transcription, can be regulated by both protein-protein interactions and mitogen-activated protein kinase (MAPK)-mediated phosphorylation (36, 41). For example, members of at least six different ETS factor subfamilies are key nuclear effectors of the Ras/Raf/MAPK pathway, serving as direct targets of MAPK phosphorylation and thus playing critical regulatory roles in cell survival and proliferation (36,41,50).Multiple lines of evidence support a causative role for ETS factors in carcinogenesis (19,36,41). The founding member of the ETS family, the v-ETS oncogene, causes hematopoetic malignancies in chickens (27). ETS factors are also associated with malignancies in humans. For example, chromosomal translocations in which the amino-terminal region of EWS is fused to the carboxy-terminal ...

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Distinct Functional Interactions of Human Skn-1 Isoforms with Ese-1 during Keratinocyte Terminal Differentiation

Cited by 31 publications

References 36 publications

Control of differentiation in a self-renewing mammalian tissue by the histone demethylase JMJD3

Control of differentiation in a self-renewing mammalian tissue by the histone demethylase JMJD3

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

The ETS Transcription Factor ESE-1 Transforms MCF-12A Human Mammary Epithelial Cells via a Novel Cytoplasmic Mechanism

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