Spatial regulation of SpMTA metallothionein gene expression in sea urchin embryos by a regulatory cassette in intron 1

Nemer, Martin; Stuebing, Elizabeth W.; Bai, Guang; Parker, Henry R.

doi:10.1016/0925-4773(94)00330-p

Cited by 17 publications

(7 citation statements)

References 36 publications

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“…The functionality of GATA elements and transcription factors in regulating the expression of these MT genes has not been examined. GATA elements are also present in several invertebrate MT genes that show highly restricted patterns of expression, including the Drosophila Mto gene (4,20) and sea urchin spMTA and spMTB genes (18,19,93). In addition, the expression patterns of the Drosophila GATA factors "serpent" and dGATA-c overlap those for Mtn and Mto (71,94,95).…”

Section: Discussionmentioning

confidence: 99%

Regulation of Metallothionein Gene Transcription

Moilanen¹,

Fukushige²,

Freedman³

1999

Journal of Biological Chemistry

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Metallothioneins are small, cysteine-rich proteins that function in metal detoxification and homeostasis. Metallothionein transcription is controlled by cell-specific factors, as well as developmentally modulated and metal-responsive pathways. By using the nematode Caenorhabditis elegans as a model system, the mechanism that controls cell-specific metallothionein transcription in vivo was investigated. The inducible expression of the C. elegans metallothionein genes, mtl-1 and mtl-2, occurs exclusively in intestinal cells. Sequence comparisons of these genes with other C. elegans intestinal cell-specific genes identified multiple repeats of GATA transcription factor-binding sites (i.e. GATA elements). In vivo deletion and site-directed mutation analyses confirm that one GATA element in mtl-1 and two in mtl-2 are required for transcription. Electrophoretic mobility shift assays show that the C. elegans GATA transcription factor ELT-2 specifically binds to these elements. Ectopic expression of ELT-2 in non-intestinal cells of C. elegans activates mtl-2 transcription in these cells. Likewise, mtl-2 is not expressed in nematodes in which elt-2 has been disrupted. These results indicate that cell-specific transcription of the C. elegans metallothionein genes is regulated by the binding of ELT-2 to GATA elements in these promoters. Furthermore, a model is proposed where ELT-2 constitutively activates metallothionein expression; however, a second metal-responsive factor prevents transcription in the absence of metals. Metallothioneins (MT)1 are a family of structurally related, low molecular weight, cysteine-rich proteins (1). The precise physiological role of MT has not been elucidated. However, evolutionary conservation across many phyla suggests that it serves important roles in cell function. Proposed roles include the following: (a) participation in maintaining the homeostasis of essential trace metals; (b) sequestration of toxic metals, such as cadmium and mercury; (c) acting as a reservoir of essential metals that can be donated to other metalloproteins; and (d) protection against intracellular oxidative damage (2).Exposure of cultured cells or whole organisms to transition metals, ionizing radiation, heat-shock, or oxidative stress induces MT transcription (1, 3-5). Metallothioneins typically occur in multigene families. The mammalian MT family consists of four members designated MT-I to MT-IV (6). It has been commented that all organisms express MT or MT-like proteins. However, not all tissues within an organism will express all MT isoforms. Numerous studies indicate that individual MT family members display specific cellular patterns of expression. Typically, MT-I and MT-II genes are coordinately expressed. It has been shown, however, that MT-2A mRNA levels do not increase in response to cadmium exposure in human proximal tubule cells (7). Expression of the human MT-I B , MT-I E , MT-I F , and MT-I G genes varies in a cell line-specific manner in response to transition metals (8 -12). Mouse MT-I is weakly exp...

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Section: Discussionmentioning

confidence: 99%

Regulation of Metallothionein Gene Transcription

Moilanen¹,

Fukushige²,

Freedman³

1999

Journal of Biological Chemistry

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“…Endogenous SpMTA gene expression is localized in aboral ectoderm of normal and metal-induced embryos and in transgenic embryos using a construct including the intron. However, if a 495-nt region of the intron including the cassette is deleted from the construct, the restricted spatial expression is largely eliminated (21). Thus, regulatory-binding sites within the inserted cassette are almost certainly responsible for spatial regulation as the same sites are in other sea urchin genes (22).…”

Section: Sea Urchin Metallothionein Intron Cassette With Invertedmentioning

confidence: 99%

DNA sequence insertion and evolutionary variation in gene regulation.

Britten

1996

Proc. Natl. Acad. Sci. U.S.A.

228

114

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Current evidence on the long-term evolutionary effect of insertion of sequence elements into gene regions is reviewed, restricted to cases where a sequence derived from a past insertion participates in the regulation of expression of a useful gene. Ten Repeated sequences were considered to be candidates for roles in the 5' regions of genes (1) and it was argued that they could move and supply evolutionary variation (2). Recent observations have shown that a number of sequences (known mobile elements and repeated sequences) were frequently inserted into the DNA of gene regions and can influence the regulation of a gene's expression. In a number of cases, the inserts contained sequences that bind nuclear proteins or the sequences were modified after insertion so that binding sites were formed that became effective parts of the regulation system for the gene. Where there is evidence that the insertions occurred far in the past, the examples show that insertion of DNA sequence elements was a source of variation leading to a useful positively selected change in gene regulation that survived a long period of evolution. Thus, this mechanism can be considered to be one of the sources of the DNA sequences that form control regions of genes. As a large amount of data has become available, genes can now be examined in which evolutionary sequence divergence has not fully obscured the evidence that an insert contributed new regulatory elements. Little is known of the evolutionary origin of the control regions, but there is growing literature (for reviews, see refs.3 and 4). Sequence change, obscuring the original structure, has occurred in the long history, and the underlying rate of base substitution that is responsible is known (5).

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“…The cis-regulatory regions of several of the Ca2+ binding Spec genes have been shown by Klein and colleagues (64,65) to contain what they term "RSR" modules, which in reporter constructs confer aboral ectoderm expression, where R is a repeated sequence and S is a sequence that contains transcription factor binding sites. In another case a "cassette" or module that includes many of the CyIIIa target sites has been identified in an intron of the sea urchin metallothionein gene, and has been shown to confer aboral ectoderm specific expression to this gene (66,67).…”

Section: Inputmentioning

confidence: 99%

Modular cis-regulatory organization of developmentally expressed genes: two genes transcribed territorially in the sea urchin embryo, and additional examples.

Kirchhamer

Yuh²,

Davidson³

1996

Proc. Natl. Acad. Sci. U.S.A.

100

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The cis-regulatory systems that control developmental expression oftwo sea urchin genes have been subjected to detailed functional analysis. Both systems are modular in organization: specific, separable fragments of the cis-regulatory DNA each containing multiple transcription factor target sites execute particular regulatory subfunctions when associated with reporter genes and introduced into the embryo. The studies summarized here were carried out on the CyIIIa gene, expressed in the embryonic aboral ectoderm and on the Endol6 gene, expressed in the embryonic vegetal plate, archenteron, and then midgut. The regulatory systems of both genes include modules that control particular aspects of temporal and spatial expression, and in both the territorial boundaries of expression depend on a combination of negative and positive functions. In both

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Spatial regulation of SpMTA metallothionein gene expression in sea urchin embryos by a regulatory cassette in intron 1

Cited by 17 publications

References 36 publications

Regulation of Metallothionein Gene Transcription

Regulation of Metallothionein Gene Transcription

DNA sequence insertion and evolutionary variation in gene regulation.

Modular cis-regulatory organization of developmentally expressed genes: two genes transcribed territorially in the sea urchin embryo, and additional examples.

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