H19 gene expression is up-regulated exclusively by stabilization of the RNA during muscle cell differentiation

Milligan, Laura; Antoine, Etienne; Bisbal, Catherine; Weber, Michaël; Brunel, Claude; Forné, Thierry; Cathala, Guy

doi:10.1038/sj.onc.1203965

Cited by 48 publications

(60 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…2 and Materials and Methods), we first analyzed nuclear matrix attachment in the mouse liver at three perinatal stages: embryonic day 15.5 and day 7.5 or 30 after birth. We have previously shown by run-on experiments that the Igf2 gene is actively transcribed in embryonic and early postnatal stages, but completely repressed after postnatal day 18 (21). Interestingly, each potential MAR at the Igf2 locus showed a specific attachment pattern (left panel of Fig.…”

Section: Resultsmentioning

confidence: 81%

See 1 more Smart Citation

Genomic Imprinting Controls Matrix Attachment Regionsin the Igf2Gene

Weber

Hagège

Murrell

et al. 2003

Molecular and Cellular Biology

Self Cite

View full text Add to dashboard Cite

Genomic imprinting at the Igf2/H19 locus originates from allele-specific DNA methylation, which modifies the affinity of some proteins for their target sequences. Here, we show that AT-rich DNA sequences located in the vicinity of previously characterized differentially methylated regions (DMRs) of the imprinted Igf2 gene are conserved between mouse and human. These sequences have all the characteristics of matrix attachment regions (MARs), which are known as versatile regulatory elements involved in chromatin structure and gene expression. Combining allele-specific nuclear matrix binding assays and real-time PCR quantification, we show that retention of two of these Igf2 MARs (MAR0 and MAR2) in the nuclear matrix fraction depends on the tissue and is specific to the paternal allele. Furthermore, on this allele, the Igf2 MAR2 is functionally linked to the neighboring DMR2 while, on the maternal allele, it is controlled by the imprinting-control region. Our work clearly demonstrates that genomic imprinting controls matrix attachment regions in the Igf2 gene.On the distal part of mouse chromosome 7, the Igf2 and H19 genes are separated by 72 kbp. At this locus, imprinting originates from paternal germ line-specific methylation that impairs the binding of a protein factor (CTCF) to the intergenic imprinting-control region (ICR). On the maternal allele, binding of CTCF results in activation of an insulator, which prevents Igf2 expression by blocking promoter access to a set of enhancers located downstream of H19 (2, 14). Thus, Igf2 gene expression is restricted to the paternal allele, whereas H19 is maternally expressed. However, Igf2 imprinting also involves additional differentially methylated regions (DMR0, DMR1, and DMR2) that control regional epigenetic modifications in a hierarchical and tissue-specific fashion (19). DMR1, located upstream of the fetal Igf2 promoters, is preferentially methylated on the paternal allele and acts as a methylation-sensitive silencer in several mesodermal tissues (5). DMR2 maps to exons 5 to 6 and augments transcription on the methylated paternal allele (24). Finally, DMR0 is maternally methylated in the placenta and overlaps the placenta-specific P0 promoter (23). All these DMRs display tissue-specific methylation patterns, and we have recently proposed that their methylation profiles are regionally coordinated through long-range chromatin interactions (19).Here, we identify intragenic AT-rich DNA sequences in the Igf2 gene that are contiguous to previously identified DMRs. These sequences have all the characteristics of matrix attachment regions (MARs) and are conserved in humans. MARs are operationally defined in MAR assays by their ability to associate to a nuclear matrix or scaffold (17) and have been implicated in the regulation of chromatin structure and gene expression. They are frequently associated with enhancers (4, 10, 11) and promote chromatin accessibility and histone acetylation (7,9,15,20,26). MARs may also sometimes act as boundaries, preventing the spreading of p...

show abstract

Section: Resultsmentioning

confidence: 81%

“…For each assay, samples were obtained from several mice, and nuclei were isolated as previously described (21). For nuclear halo preparation, we adapted a procedure from the NaCl method (22) (see below).…”

Section: Methodsmentioning

confidence: 99%

Genomic Imprinting Controls Matrix Attachment Regionsin the Igf2Gene

Weber

Hagège

Murrell

et al. 2003

Molecular and Cellular Biology

Self Cite

View full text Add to dashboard Cite

show abstract

“…Nuclear Run-on Analysis-Nuclei were isolated from the livers of p8 neonates and prepared as described (26). Briefly, the liver was homogenized in chilled buffer containing 2.1 M sucrose, 10 mM HEPES, pH 7.6, 2 mM EDTA, 15 mM KCl, 10% glycerol, 150 mM spermine, 500 mM dithiothreitol, 500 mM phenylmethylsulfonyl fluoride, and 7 g/ml aprotinin.…”

Section: Methodsmentioning

confidence: 99%

Imprint Control Element-mediated Secondary Methylation Imprints at the Igf2/H19 Locus

Srivastava

Frolova

Rottinghaus

et al. 2003

Journal of Biological Chemistry

View full text Add to dashboard Cite

Understanding the molecular basis of monoallelic expression as observed at imprinted loci is helpful in understanding the mechanisms underlying epigenetic regulation. Genomic imprinting begins during gametogenesis with the establishment of epigenetic marks on the chromosomes such that paternal and maternal chromosomes are rendered distinct. During embryonic development, the primary imprint can lead to generation of secondary epigenetic modifications (secondary imprints) of the chromosomes. Eventually, either the primary imprints or the secondary imprints interfere with transcription, leading to parent-of-origin-dependent silencing of one of the two alleles. Here we investigated several aspects pertaining to the generation and functional necessity of secondary methylation imprints at the Igf2/H19 locus. At the H19 locus, these secondary imprints are, in fact, the signals mediating paternal chromosome-specific silencing of that gene. We first demonstrated that the H19 secondary methylation imprints are entirely stable through multiple cell divisions, even in the absence of the primary imprint. Second, we generated mouse mutations to determine which DNA sequences are important in mediating establishment and maintenance of the silent state of the paternal H19 allele. Finally, we analyzed the dependence of the methylation of Igf2DMR1 region on the primary methylation imprint about 90 kilobases away.

show abstract

“…Nuclear run-ons were performed as described previously (Milligan et al, 2000) with some modifications. Equal amounts (10 7 cpm/ml) of labeled nuclear RNA were hybridized at 651C for 24 h to Zeta-probe membranes (Bio-Rad) previously bound with 5 mg of linearized plasmid DNAs.…”

Section: Cell Culturementioning

confidence: 99%

Mechanisms underlying differential expression of interleukin-8 in breast cancer cells

et al. 2004

View full text Add to dashboard Cite

We have recently reported that interleukin-8 (IL-8) expression was inversely correlated to estrogen receptor (ER) status and was overexpressed in invasive breast cancer cells. In the present study, we show that IL-8 overexpression in breast cancer cells involves a higher transcriptional activity of IL-8 gene promoter. Cloning of IL-8 promoter from MDA-MB-231 and MCF-7 cells expressing high and low levels of IL-8, respectively, shows the integrity of the promoter in both cell lines. Deletion and site-directed mutagenesis of the promoter demonstrate that NF-jB and AP-1 and to a lesser extent C/EBP binding sites play a crucial role in the control of IL-8 promoter activity in MDA-MB-231 cells. Knockdown of NF-jB and AP-1 activities by adenovirusmediated expression of an NF-jB super-repressor and RNA interference, respectively, decreased IL-8 expression in MDA-MB-231 cells. On the contrary, restoration of Fra-1, Fra-2, c-Jun, p50, p65, C/EBPa and C/EBPb expression levels in MCF-7 cells led to a promoter activity comparable to that observed in MDA-MB-231 cells. Our data constitute the first extensive study of IL-8 gene overexpression in breast cancer cells and suggest that the high expression of IL-8 in invasive cancer cells requires a complex cooperation between NF-jB, AP-1 and C/EBP transcription factors.

show abstract

H19 gene expression is up-regulated exclusively by stabilization of the RNA during muscle cell differentiation

Cited by 48 publications

References 48 publications

Genomic Imprinting Controls Matrix Attachment Regionsin the Igf2Gene

Genomic Imprinting Controls Matrix Attachment Regionsin the Igf2Gene

Imprint Control Element-mediated Secondary Methylation Imprints at the Igf2/H19 Locus

Mechanisms underlying differential expression of interleukin-8 in breast cancer cells

Contact Info

Product

Resources

About