Identification of CpG island at the 5' end of murine leukemia inhibitory factor gene

Kašpar, Petr; Dvořák, Michal; Bartůněk, Petr

doi:10.1016/0014-5793(93)80058-3

Cited by 5 publications

(6 citation statements)

References 19 publications

(8 reference statements)

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“…The first region is located between the D-form axon and the M-form exon and is characterized by a high-GC content and regions of sequencing similarity to the human LIF gene. In addition, Kaspar et al (1993) have demonstrated that this region of the LIF gene is hypomethylated in many types of cells and associates with specific nuclear proteins. The authors have argued that the GC-rich region has the properties expected of a CpG 'island' found in the promoter region of many genes.…”

Section: Discussionmentioning

confidence: 99%

“…The region therefore confers an important requirement for specific genomic locations to permit expression of the LIF gene. The identification of hypomethylated regions in the endogenous LIF gene in this region and binding sites for nuclear proteins (Kaspar et al, 1993) suggest that the action of these proteins may be to repress transcription. It is of interest that the nuclear protein factor has been demonstrated to bind to hypomethylated regions in the GC islands and act to repress transcription Bird, 1991, 1992).…”

Section: Discussionmentioning

confidence: 99%

“…The M-LIF exon is located 463 nucleotides 3' of the D-LIF exon. The region between the D-LIF exon and the M-LIF exon is characterized by a high concentration of GC nucleotides, significant regions of sequence conservation between the mouse and human LIF genes and a high density of the recognition sites for the methylation-sensitive restriction enzyme HpaII (Stahl et al, 1990;Kaspar et al, 1993; Figure 1). The region between the D-LIF exon and the M-LIF exon also contains a 41 bp polypyrimidine tract.…”

Section: Dna Sequence Of the Lif Genementioning

confidence: 99%

“…These studies reveal that the LIF gene contains two principal genetic regulatory elements: a 5' distal enhancer region, which is required for expression of both M-LIF and D-LIF transcripts, and a second element, located between the D-LIF and M-LIF transcriptional initiation sites, the major activity of which has been defined as promoting expression of the LIF gene depending on its genomic location. This region has been shown to be subject to hypomethylation in cultured cells in vitro (Kaspar et al, 1993). In addition, DNA sequence analysis of the LIF gene and its surrounding DNA sequences has revealed the location of regions in the 5' distal control element that may be involved in regulation of the LIF gene by maternal steroid hormones.…”

Section: Introductionmentioning

confidence: 99%

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Identification of two elements involved in regulating expression of the murine leukaemia inhibitory factor gene

Hsu

Heath

1994

Biochemical Journal

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Mouse leukaemia inhibitory factor (LIF) is a polyfunctional cytokine which exhibits multiple functions in vitro and in vivo. Two forms of LIF cDNA, differing at their 5' ends, have been described encoding either diffusible (D-LIF) or matrix-associated (M-LIF) forms of the protein [Rathjen, Toth, Willis, Heath and Smith (1990) (Cell 62, 1105-1114]. The present report describes the DNA sequence and functional characterization of the murine LIF gene and its surrounding transcriptional regulatory elements. Transient transfection of constructs containing the LIF gene and various amounts of 5'-non-coding sequence failed to give detectable levels of expression, suggesting the presence of inhibitory sequences within the LIF gene. Stable cell lines were produced by transfection of experimental constructs containing various lengths of 5'-non-coding sequence of the LIF gene, or the heterologous phosphoglycerate kinase promoter, linked to an LIF/neomycin-resistance-hybrid-coding sequence. The frequency of recovery of stable clones indicated that sequences located in the first intron between the transcriptional start sites for D-LIF and M-LIF act to suppress expression of the gene in most genomic locations. This region is rich in GC residues and has been shown to be hypomethylated in vitro [Kaspar, Dvorak and Bartunek (1993) FEBS Lett. 319, 159-162]. Analysis of the LIF/neomycin-resistance transgene expression in these stable cell clones demonstrated that transcripts containing the M-LIF or D-LIF exons required the presence of sequences located between -1200 and -3200 in the LIF gene. In the absence of these sequences, transcription is initiated elsewhere within the first intron. These sequences can be replaced by the heterologous phosphoglycerate kinase promoter. Deletion of the GC-rich region between the D-LIF and M-LIF transcriptional start sites results in the appearance of transcripts that do not splice out the first intron of the LIF gene. These may result from gene or promoter trapping of the LIF gene. Sequence analysis of the region between -1200 and -3200 revealed a number of minimal steroid-response elements, regions of similarity to DNAase I-hypersensitive sites in the uteroglobin gene and a region of alternating purine/pyrimidine sequence. This study therefore defines two important regulatory regions in the LIF gene: a GC-rich region in the first intron and a distal 'enhancer' located between -3200 and -1200.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Dna Sequence Of the Lif Genementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Identification of two elements involved in regulating expression of the murine leukaemia inhibitory factor gene

Hsu

Heath

1994

Biochemical Journal

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“…This observation has at least two important implications. First, CpG islands are gene-associated and can be used as markers to identify genes [8][9][10][11][12][13][14][15]. For example, according to the results in [15], about 70% of the identi_ed CpG islands are associated with the human genes.…”

Section: Cpg Dinucleotides and Methylationmentioning

confidence: 99%

Locating CpG Islands with Kullback-Leibler Divergence

Chen¹

2012

J Biomet Biostat

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A CpG island is a short contiguous DNA subsequence that is rich in CG dinucleotides. CpG islands are often located around the promoters of housekeeping genes and have been found associated with certain tissue-specific genes. This observation indicates that they can be used as markers to identify genes. The information about the locations of CpG islands can also help us understand a gene regulation process called methylation. In this report, we propose a statistical method for locating CpG islands. Our method employs the Kullback-Leibler divergence. We use the given DNA sequence to determine a window size and a shift size for computing the divergence values along a DNA segment. A region in the proximity of a CpG island should contain consecutive windows with high divergence values. The distribution of the Kullback-Leibler divergence values can be suitably fitted by a truncated Pareto distribution. We estimate the parameters of the truncated Pareto distribution via the maximum likelihood principle. Then the fitted distribution is applied to locate regions with a divergence value exceeding a threshold level of significance. To assess the accuracy of our method, we compare our results to the putative CpG islands found in four well-studied mouse and human DNA sequences. The comparison suggests our approach consistently yields reliable predictions of CpG island locations.

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Sequencing of the rat light neurofilament promoter reveals differences in methylation between expressing and non-expressing cell lines, but not tissues

Reeben

Myöhänen

Saarma

et al. 1995

Gene

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Identification of CpG island at the 5' end of murine leukemia inhibitory factor gene

Cited by 5 publications

References 19 publications

Identification of two elements involved in regulating expression of the murine leukaemia inhibitory factor gene

Identification of two elements involved in regulating expression of the murine leukaemia inhibitory factor gene

Locating CpG Islands with Kullback-Leibler Divergence

Sequencing of the rat light neurofilament promoter reveals differences in methylation between expressing and non-expressing cell lines, but not tissues

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