PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “noncoding RNA”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 505 records · Page 28Linked to original sources
PubMed2003

Folate treatment and unbalanced methylation and changes of allelic expression induced by hyperhomocysteinaemia in patients with uraemia.

BACKGROUND: Hyperhomocysteinaemia occurs in several genetically determined and acquired disorders and is highly prevalent in patients with uraemia. In these disorders, homocysteine precursor S-adenosylhomocysteine, a powerful competitive inhibitor of S-adenosylmethionine-dependent methyltransferases, is increased, suggesting unbalanced methylation. We aimed to investigate whether DNA hypomethylation is present in patients with uraemia who also have hyperhomocysteinaemia and whether regulation of specific classes of genes, dependent on DNA methylation, is compromised. METHODS: We selected men with hyperhomocysteinaemia and uraemia who were having standard haemodialysis treatment, and compared them with healthy male controls. We measured the homocysteine concentration from plasma samples and obtained DNA and RNA samples from peripheral mononuclear cells. DNA methylation was assessed by cytosine extension assay and by Southern blotting. Allelic expression of pseudoautosomal and imprinted genes was investigated by analysis of suitable restriction fragment length polymorphisms. FINDINGS: Total DNA hypomethylation was higher in patients than in controls (z score -4.593, p=0.0006) and allelic expression was changed in both sex-linked and imprinted genes. The shift from monoallelic to biallelic expression was dependent on homocysteine concentrations. Folate therapy, a common method to reduce hyperhomocysteinaemia, restored DNA methylation to normal levels and corrected the patterns of gene expression. INTERPRETATION: Our results suggest that hyperhomocysteinaemia affects epigenetic control of gene expression, which can be reverted by folate treatment. Our data support the hypothesis that the toxic action of homocysteine can be mediated by macromolecule hypomethylation.

Adult↗
PubMed2004

XIST unmethylated DNA fragments in male-derived plasma as a tumour marker for testicular cancer.

Testicular germ-cell tumours (TGCTs) are the most common malignant diseases among men aged 20-40 years. We developed a DNA tumour marker for TGCTs based on the unmethylated DNA profile of a neoplasm. The 5' end of the XIST gene is mainly hypomethylated in TGCTs irrespective of XIST expression. Male somatic cells, however, show complete methylation through the CpG sites, including the minimum promoter and XIST-conserved repeats. Identification of a XIST unmethylated fragment in male plasma might be diagnostic for TGCTs.

Biomarkers, Tumor↗
PubMed2004

Genomic imprinting in disruptive spermatogenesis.

The possibility of imprinting disease transmission by assisted reproductive technologies has been raised after births of children with Angelman's and Beckwith-Wiedemann's syndromes. To investigate whether imprinting defects were associated with disturbed spermatogenesis, we studied two oppositely imprinted genes in spermatozoan DNA from normozoospermic and oligozoospermic patients. In the mesodermal specific transcript gene (MEST), bisulphite genomic sequencing showed that maternal imprinting was correctly erased in all 123 patients. However, methylation of the H19 gene did not change in any of 27 normozoospermic individuals (0%, 95% CI 0-13%), compared with methylation changes in eight moderate (17%, 8-31%, p=0.026) and 15 severe (30%, 18-45%, p=0.002) oligozoospermic patients. Our data suggest an association between abnormal genomic imprinting and hypospermatogenesis, and that spermatozoa from oligozoospermic patients carry a raised risk of transmitting imprinting errors.

Alleles↗
PubMed1997

Association of IGF2 and H19 imprinting with choriocarcinoma development.

We studied IGF2 and H19 expression, and methylation status of H19 gene in androgenetic moles and choriocarcinomas. The human placentae were examined similarly as a control. The CpG sites analyzed for methylation covered the 5' portion and the entire coding regions of H19. Although the paternal IGF2 and the maternal H19 allele were exclusively transcribed in full-term placentae, both H19 alleles were active in early placentate of 6-8 weeks gestation. The level of H19 expression in the mole was similar to that in normal placentae, which is compatible with the finding that half of the H19 gene was methylated and the remaining one was hypomethylated en masse in the complete mole. These imply the importance of regulating the level of H19 transcription not only for normal embryogenesis but also for the development of androgenetic moles. Choriocarcinomas were characterized by a low expression of IGF2 and a high expression of H19 with the transcripts being apparently intact in size. Biallelic expression of IGF2 or H19 was found frequently but not consistently in choriocarcinomas. Contrary to expectation, enhanced H19 expression was accompanied by hypermethylation of CpG sites over the entire gene region, apparently being at variance with the finding in normal placentae and androgenetic moles. The hypermethylation of CpG sites was also recognized in choriocarcinoma specimens surgically removed. The active H19 allele was unmethylated in placentae and probably so in androgenetic moles, but it was heavily methylated in choriocarcinomas. These findings provide the possibility that the mutated promoter is responsible for overcoming transcriptional suppression by CpG methylation in the H19 gene.

Blotting, Southern↗
PubMed2001

Epigenetic mark sequence of the H19 gene in human sperm.

We have investigated the epigenetic mark in the human H19 gene. The H19 promoter is methylation-free in human sperm, but it is methylated in the paternally derived allele of most adult tissues. Consequently, the H19 gene is exclusively transcribed from the maternal allele. It was demonstrated that the differentially methylated region (DMR) located 2 kb upstream from mouse H19 is essential for the imprinting of H19. A 39 bp sequence in DMR has a high degree of similarity between humans, mice and rats. The highly conserved 15 bp core region of the consensus sequence contains four methylatable sites, and thus has been proposed as a potential imprinting mark region. In this study, fine epigenetic sequencing analysis was performed on the sperm DNA in comparison with other adult organs. Interestingly, the conserved sequence of the potential mark region was methylated in almost all the sperm genomes analyzed. Furthermore, the single dinucleotide CpG, whose methylation affects the accessibility of the element to CTCF, was methylated in the conserved core in the human sperm. These results suggest that the human core sequences may act as an imprinting center in the reciprocal monoallelic expression of H19.

Adult↗
PubMed2003

H19 and Igf2--enhancing the confusion?

Genomic imprinting, whereby certain genes are expressed dependent on whether they are maternally or paternally inherited, is restricted to mammals and angiosperm plants. This unusual mode of gene regulation results from the complex interplay between cis-regulatory elements, leading to parent-of-origin-dependent epigenetic modifications and tissue-specific patterns of imprinted gene expression. Many studies of imprinting and imprinted genes have focused on epigenetic effects, such as DNA methylation and chromatin structure. However, it is equally important to explore the interconnected role of regulatory elements at imprinted domains by genetic experiments, including the use of transgenes and deletions.

Animals↗
PubMed2002

X-chromosome inactivation: closing in on proteins that bind Xist RNA.

X inactivation is the developmentally regulated silencing of a single X chromosome in XX female mammals. In recent years, the Xist gene has been revealed as the master regulatory switch controlling this process. Parental imprinting and/or counting mechanisms ensure that Xist is expressed only on the inactive X chromosome. Chromosome silencing then results from the accumulation of the Xist RNA silencing signal, in cis, over the entire length of the X chromosome. A key issue has been to identify the factors that interact with Xist RNA to initiate heritable gene silencing. This review discusses recent progress that has put this goal in sight.

Animals↗
PubMed1997

DNA methylation and imprinting: why bother?

DNA methylation is crucial for mammalian development because embryos that cannot maintain normal methylation levels die after gastrulation. I propose that DNA methylation is only important for the somatic lineages, but has no role in embryonic lineages including the germ line. Among vertebrates, genomic imprinting is found only in mammals, and numerous hypotheses have ascribed an essential function to imprinting because of the uniquely mammalian developmental and physiological requirements. However, our understanding of molecular details of the imprinting process, as well as evolutionary considerations, is rather consistent with imprinting having no intrinsic role in mammalian development.

Animals↗
PubMed1997

Imprinting in clusters: lessons from Beckwith-Wiedemann syndrome.

Imprinted genes in mammals can be clustered in the genome. This raises important questions about mechanistic and functional relationships between imprinted genes in a cluster. The insulin-like growth factor II (IGF2) gene is paternally expressed and is surrounded by maternally expressed genes. Loss of imprinting of IGF2 is the most common molecular defect found in the human foetal overgrowth syndrome, Beckwith-Wiedemann syndrome (BWS). Transgenic experiments in the mouse establish that overexpression of IGF2 can result in most of the symptoms of BWS. However, mutations, translocations, or methylation defects in BWS have so far been found in three of the linked maternally expressed genes. We present a model where the paternal growth enhancer IGF2 is surrounded by multiple maternal suppressors, and mutations, or epigenetic alterations, in any of these suppressors could cause BWS. In addition, the precise phenotypic spectrum of BWS might depend on which maternally expressed gene is mutated.

Animals↗
PubMed1999

Isolation of sex-specific cDNAs from fetal mouse brain using mRNA differential display and representational difference analysis.

Comparing female and male brain structures reveals a variety of sex differences in many vertebrates. These differences are manifested throughout the brain, in regions such as the hypothalamus, the preoptic area and the amygdala. Some are thought to be induced during the fetal period by the effect of steroid hormones produced in the gonads. It is well-established that fetal androgens, probably through the conversion to estrogen by the enzyme aromatase, masculinize the nervous system and set adult mounting behavior in rodents. However, less is known about molecular mechanisms involved in gender-specific development of the brain. We have taken a broad approach to isolate sex-specific genes from fetal brain. mRNAs from 18.5 days post-coitum (dpc) female and male mouse brain were screened with the classical and the recently developed signal peptide differential display (SPDD) and with representational difference analysis of cDNA (cDNA-RDA). Two sex-specific cDNAs were isolated, F29 and M17, corresponding to the female-specific Xist gene and the male-specific Smcy gene, respectively.

Amino Acid Sequence↗
PubMedDate not supplied

DNA methylation, chromatin boundaries, and mechanisms of genomic imprinting.

In mammals, the maternal and paternal genomes are both required for normal embryonic and postnatal development. As a consequence, the majority of genes possess a bi-allelic pattern of expression, with the exception of certain loci where transcription is strictly dependent on parental origin. This alternative, termed genomic imprinting, is an epigenetic form of gene regulation that allows controlled expression of one parental allele. Experimental evidence supports the idea that chromatin organization, DNA methylation, replication timing, genomic domain organization, and more recently methylation-dependent boundary function are key components of imprinting mechanisms. Imprinted genes are mainly required during embryogenesis and development, but loss of controlled imprinting has direct consequences in carcinogenesis. For example, imprinted tumor suppressor genes and proto-oncogenes are highly susceptible to allelic inactivation or in contrast to activation that induces tumorigenic processes. Therefore, genomic imprinting represents one of the more challenging and interesting scientific and medical topics, and especially because a large combinatorial set of possibilities for gene regulation arises from the increasing number of imprinted loci identified.

Alleles↗
PubMed2001

Sequence analysis of the MHC class I region reveals the basis of the genomic matching technique.

The genomic matching technique (GMT) improves survival following bone marrow transplantation (BMT) between unrelated donor and recipient pairs correlating with a decrease in incidence and severity of graft-versus-host disease (GvHD). The principles of this technique are based on the duplication and polymorphic characteristics of the major histocompatibility complex (MHC). Specifically, the beta block GMT matches for a 300 kb region that contains the human leukocyte antigen (HLA-B and -C) genes as well as other non-HLA genes such as the natural killer cell receptor ligand PERB11 (MIC). The block contains two large segmental duplications. One results in two PERB11 genes (11.1 and 11.2), the other in two class I genes (HLA-B and -C). With the complete sequencing of the class I region of the MHC in different haplotypes, we can now show that the beta block GMT profiles reflect amplification of the duplicated PERB11 segments and not the duplicated segments containing HLA-B and -C, and yet provide a signature that characterizes the entire block rather than individual loci.

Base Sequence↗