elt-2, a Second GATA Factor from the Nematode Caenorhabditis elegans

Hawkins, M.; McGhee, James D.

doi:10.1074/jbc.270.24.14666

Cited by 81 publications

(56 citation statements)

References 31 publications

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“…Intestinal cell-specific expression of many C. elegans genes, including those encoding the vitellogenins, gut carboxylesterase, metalinducible mtl-1 and mtl-2, P-glycoprotein, GATA-binding transcription factor-2, and aspartic acid and cysteine proteases, is dependent on the presence of one or more copies of UREs designated GATA elements (65)(66)(67)(68)(69)(70)(71). These elements are binding sites for members of the GATA family of transcription factors (69,72). In C. elegans, GATA elements that are responsible for controlling intestinal cell-specific transcription have the consensus sequence (A/T)GATA(A/G).…”

Section: Discussionmentioning

confidence: 99%

Molecular Characterization of a Novel, Cadmium-inducible Gene from the Nematode Caenorhabditis elegans

Liao¹,

Dong²,

Freedman³

2002

Journal of Biological Chemistry

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Cadmium is an environmental contaminant that is both a human toxicant and carcinogen. To inhibit cadmium-induced damage, cells respond by increasing the expression of genes that encode stress-response proteins. We previously reported the identification of 48 cadmium-inducible mRNAs in the nematode Caenorhabditis elegans. Here we describe a new cadmium-responsive gene, designated cdr-1, whose rate and level of inducible expression parallel those of the C. elegans metallothioneins. The CDR-1 mRNA contains an open reading frame of 831 bp and encodes a predicted 32-kDa, integral membrane protein. Following cadmium exposure, cdr-1 is transcribed exclusively in intestinal cells of post-embryonic C. elegans. In vivo, the CDR-1 protein is targeted specifically to the intestinal cell lysosomes. cdr-1 transcription is significantly induced by cadmium but not by other tested stressors. These results indicate that cdr-1 expression is regulated by cadmium and in a cell-specific fashion. Inhibition of CDR-1 expression renders C. elegans susceptible to cadmium toxicity. In conclusion, cdr-1 defines a new class of cadmium-inducible genes and encodes an integral membrane, lysosomal protein. This protein functions to protect against cadmium toxicity.The transition metal cadmium is considered a serious occupational and environmental health threat. It is continuously introduced into the atmosphere through the smelting of ores and the burning of fossil fuels and is commonly found in "Superfund" clean-up sites (1-3). Humans are exposed to cadmium primarily via inhalation and the ingestion of cadmium-containing foods (4). Toxicological responses of cadmium exposure include kidney damage, respiratory diseases, neurological disorders, and lung, kidney, prostate, and testicular cancers (4).Cadmium induces intracellular damage via the (a) nonspecific inactivation/denaturation of proteins, by binding to free sulfhydryl residues; (b) displacement of zinc co-factors from a variety of proteins, including transcription factors; and (c) generation of reactive oxygen species, which ultimately oxidize DNA, proteins, and lipids. Although cadmium itself is not redox active in vivo and cannot directly catalyze the reduction of molecular oxygen, it has been suggested that the production of reactive oxygen species is a consequence of a cadmium-induced depletion of cellular glutathione or the inactivation of copper/ zinc-superoxide dismutase (5, 6).To attenuate the toxic effects of cadmium, cells respond by increasing the steady-state levels of a variety of proteins. The functions of these proteins can be broadly defined, because those that repair intracellular damage or those that remove the toxicants (e.g. cadmium, reactive oxygen species). To remove toxicants, cells activate the transcription of genes that encode proteins that are involved in scavenging reactive oxygen species, including heme oxygenase, ␥-glutamylcysteine synthetase, superoxide dismutase, catalase, glutathione peroxidase, and glucose-6-phosphate dehydrogenase (7-11). Cadmium is esse...

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Section: Discussionmentioning

confidence: 99%

Molecular Characterization of a Novel, Cadmium-inducible Gene from the Nematode Caenorhabditis elegans

Liao¹,

Dong²,

Freedman³

2002

Journal of Biological Chemistry

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confidence: 99%

“…This endoderm specification step takes place in the E cell, the clonal progenitor of the intestine, within a permissive environment associated with lowered nuclear levels of the HMG protein POP-1 (Lin et al 1995(Lin et al , 1998Rocheleau et al 1997;Thorpe et al 1997;Lo et al 2004). The END-1/END-3 pair of GATA factors is proposed to directly activate expression of the elt-2 gene, which encodes a GATA factor that may be the principal transcription factor directing subsequent intestinal differentiation (Hawkins and McGhee 1995;Fukushige et al 1998Fukushige et al , 2005.The properties of the med genes have generated substantial interest for at least two reasons: (i) they are proposed to occupy the important interface between maternal and zygotic control of gene expression ( both MS mesoderm and E endoderm has been used as evidence for an ancient ''mesendoderm'' region of the embryo, specified by a transcription factor network conserved in all bilateral metazoons (Maduro et al 2001;Rodaway and Patient 2001;Maduro and Rothman 2002;Broitman-Maduro et al 2005). Maduro et al (2001, p. 481) have proposed that ''the meds are activated by, and function downstream of, SKN-1 in the EMS lineage and are essential to specify E and MS fates in any context.''…”

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confidence: 99%

Reevaluation of the Role of the med-1 and med-2 Genes in Specifying the Caenorhabditis elegans Endoderm

Goszczynski

McGhee

2005

Genetics

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The med-1 and med-2 genes encode a pair of essentially identical GATA factor-related transcription factors that have been proposed to be necessary for specification of the C. elegans endoderm (intestine or E lineage) as well as part of the C. elegans mesoderm. med-1 and med-2 are proposed to be the direct downstream targets and the principal effectors of the maternally provided SKN-1 transcription factor; med-1 and med-2 would thus occupy the pivotal interface between maternal and zygotic control of gene expression. The conclusion that med-1 and med-2 are necessary for C. elegans endoderm specification was based on a partially penetrant (50%) loss of endoderm markers produced by RNA-mediated interference (RNAi). To determine whether this partial penetrance reflects: (i) inefficient RNAi against early zygotic transcripts, (ii) experimental uncertainty in the expected level of endoderm loss in skn-1 nulls, or (iii) additional redundancy in the pathway of endoderm specification, we constructed worm strains that segregate embryos lacking both the med-1 gene (because of a gene-specific deletion) and the med-2 gene (using either of two chromosomal deficiencies). Contrary to expectations, we observe that only 3-20% of med-2(ÿ); med-1(ÿ) embryos do not express markers of endoderm differentiation. Furthermore, we found no evidence for a maternal contribution of the med genes to endoderm specification. We conclude that the major pathway(s) for endoderm specification in C. elegans must be independent of the med-1 and med-2 genes. T HE Caenorhabditis elegans endoderm (intestine or E lineage) is clonally derived from a single cell, the E cell, in the eight-cell embryo (Sulston et al. 1983). The early endoderm is one of the few C. elegans lineages for which a plausible specification pathway has been proposed in molecular detail, beginning with maternally provided transcription factors, progressing through several waves of zygotically produced transcription factors, and ending with gene products that function in the terminally differentiated intestine (see review by Maduro and Rothman 2002; see also Baugh et al. 2003Baugh et al. , 2005Robertson et al. 2004). Figure 1 summarizes the regulatory cascade proposed for specification of the C. elegans endoderm. The maternally provided b-ZIP-like transcription factor SKN-1 is essential for correct specification of the fate of the EMS blastomere of the four-cell embryo (Bowerman et al. 1992(Bowerman et al. , 1993. Within the EMS cell, SKN-1 is proposed to directly activate the zygotic expression of two genes called med-1 and med-2, which encode zinc-finger proteins related to GATA-type transcription factors but with atypical binding sites (Maduro et al. 2001;Maduro and Rothman 2002;Broitman-Maduro et al. 2005).These two small intronless genes are 98% identical and, for convenience, are often referred to simply as the med genes (mesendoderm-determining); they are the principal subjects of this article. The med genes are proposed to specify both the C. elegans endoderm and that p...

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“…These results suggest that CE1(bs258) could be involved in gene transcription. However, the GATA factors-binding site (A/T)GATA(A/T) such as it has been described in C. elegans (Shim et al,1995;Hawkins and McGhee, 1995;Gilleard and McGhee, 2001) was not completely conserved within CE1(bs258), suggests that the GATA factor could not recognize these sites. Heat shock factors-binding sites are also contained into CeRep16, a member of the C. elegans repetitive DNA family (Jones et al, 1986), suggests that some repetitive DNA elements function to gene expression and supports the present hypothesis that the CE1 family can be a "genomic reservoir" for functional DNA sites (see Section 4.2).…”

Section: Ce1(bs258) Forms a Hairpin Structure And Binds To Many Regulmentioning

confidence: 99%

A novel non-coding DNA family in Caenorhabditis elegans

Takashima

Bando

Kagawa

2007

Gene

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A novel non-coding DNA family in Caenorhabditis elegansKeywords: repetitive element; palindrome; gene/element association; enhancer; genome organization. -2 - Yasuo AbstractMany repetitive elements, for example, SINEs, LINEs, LTR-retrotransposons and other SSRs are dispersed throughout eukaryotic genomes. To understand the biological function of these repetitive elements is of great current research interest. In this study, we report on the identification of a novel non-coding DNA family, designated CE1 family, in the nematode C. elegans genome. Some CE1 elements constituted a large palindrome sequence. The CE1 elements were interspersed at 95 sites in the C. elegans genome. Most of the CE1 elements were associated with, or are within, protein-coding genes. The sequence of the CE1 elements indicated that some could form a hairpin structure. One of the CE1 family, CE1(bs258), is located in the first intron of a novel gene, C46H11.6 which encodes a PDZ/DHR/GLGF domain protein. In gfp and lacZ reporter gene assays the CE1(bs258) element appeared to behave as an enhancer element for the expression of C46H11.6 but no effect on the expression of the opposite direction gene, pat-10 which encodes the body-wall muscle troponin C. The CE1(bs258) RNA transcript was detected by RT-PCR even when CE1(bs258) was located in an intron. We conclude that CE1 elements are involved in the expression of adjacent genes and are therefore selectively retained in the C. elegans genome. We discussed a biological function of the CE1(bs258) having many transcription factor-binding sites.-3 -

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elt-2, a Second GATA Factor from the Nematode Caenorhabditis elegans

Cited by 81 publications

References 31 publications

Molecular Characterization of a Novel, Cadmium-inducible Gene from the Nematode Caenorhabditis elegans

Molecular Characterization of a Novel, Cadmium-inducible Gene from the Nematode Caenorhabditis elegans

Reevaluation of the Role of the med-1 and med-2 Genes in Specifying the Caenorhabditis elegans Endoderm

A novel non-coding DNA family in Caenorhabditis elegans

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