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47-571: H19 or H-19 may refer to: H19 (gene) , a maternally-transmitted human gene British NVC community H19 , a type of heath community in the British National Vegetation Classification Heathkit H19 , a serial terminal used with the Heathkit H8 microcomputer Highway H19 (Ukraine) HMS  H19 , an H-class submarine ordered by but not commissioned into

94-426: A n/a n/a n/a n/a n/a H19 is a gene for a long noncoding RNA , found in humans and elsewhere. H19 has a role in the negative regulation (or limiting) of body weight and cell proliferation . This gene also has a role in the formation of some cancers and in the regulation of gene expression . The H19 gene is expressed exclusively on one parental allele in a phenomenon known as imprinting . H19

141-571: A trans -activation potential. Phosphorylation of C/EBPβ can have an activation or a repression effect. For example, phosphorylation of threonine 235 in human C/EBPβ, or of threonine 188 in mouse and rat C/EBPβ, is important for C/EBPβ trans -activation capacity. Phosphorylation(s) of C/EBPβ in its regulatory domain can also modulate its function. It was shown in C. elegans that multiple cis elements of cebp-1 mRNA 3'UTR interact with mak-2 to upregulate expression of CEBP-1 in neuronal development. C/EBPβ and δ are transiently induced during

188-558: A DNA construct strongly inhibited transcription of the H19 gene. In cell lines derived from human choriocarcinomas, Kopf et al. found that transcription of H19 was under the simultaneous control of both a 5’ upstream and a 3’ downstream region. Kopf et al. have suggested that this simultaneous and bidirectional regulation of H19 may involve a member of the AP2 transcription factor family. H19 gene transcription has also been shown to be activated by

235-466: A cell membrane efflux pump commonly found in multidrug resistant cells; instead, they overexpress a 95kD membrane glycoprotein p95. p95, or NCA-90, is related to carcinoembryonic antigens , which have been found to reduce drug toxicity by Kawaharata et al. Ccaat-enhancer-binding proteins C/EBP proteins interact with the CCAAT ( cytosine -cytosine- adenosine -adenosine- thymidine ) box motif, which

282-418: A demethylating agent, grow much slower than cells cultured in the absence of Azad. At the same time, H19 expression increases while IGF2 expression decreases in the presence of Azad. The reduction of IGF2 expression could be a reason for the slower growth of cells treated with Azad. As well, in a mouse bladder carcinoma cell line, where transfection of a human H19 DNA construct results in high expression of H19,

329-411: A direct link between H19 expression and the amount of DNA within the cell. In contrast to most other cancers, adrenocortical neoplasms appear to have decreased expression of H19. To determine a possible cause for the downregulation of H19, Gao et al. studied the methylation of 12 CpG sites in the H19 promoter in normal, hyperplasia, adenoma and carcinoma adrenals. They found that in carcinomas, there

376-506: A heavily methylated H19 promoter with enhanced H19 expression. This led researchers Arima et al. to suggest that in cases of choriocarcinomas, the H19 promoter was mutated, allowing it to overcome the transcriptional repression of promoter CpG methylation. In hepatocellular carcinoma , the expression of H19 and IGF2 usually changes from monoallelic to biallelic. In in vitro studies, culturing hepatocellular carcinoma cell lines in hypoxic condition upregulated H19 expression. Whether or not

423-542: A loss of H19 function express an overgrowth phenotype similar to babies with BWS . This has led researchers to suggest that perhaps the only function of H19 RNA expression is to regulate the expression of IGF2 (Insulin Growth Factor 2). Overexpression of IGF2 can be responsible for overgrowth, and generally, IGF2 is expressed in the absence of H19. Mouse embryos overexpressing H19 tend to die between embryonic day 14 and birth. Brunkow et al. have suggested two reasons for

470-474: A part of the sequence that has shown no transcriptional activity in deletion assays. As a result, these Sp1 binding sites are not expected to contribute much to the regulation of H19 gene transcription. The H19 gene sequence also contains binding sites for the C/EBP family of transcription factors. One of these C/EBP transcription factor binding sites also contains a CpG site. In vitro methylation of this CpG site on

517-447: A role in neurodegenerative pathogenesis. Genetic and molecular pathways with degenerative implications involving C/EBPβ and its homologs are conserved across multiple model organisms including Mus musculus, Drosophila melanogaster, Caenorhabditis elegans, and Danio rerio . Upstream regulators of C/EBPβ include genes known to be associated with neurodegenerative and neurodevelopmental disease when mutated or dysregulated. This includes

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564-767: A tumor suppressor in pancreatic ductal adenocarcinoma. This is of particular interest since only few tumor suppressors have been identified in the context of pancreatic cancer. The function of CCAAT/enhancer-binding proteins in cancer is thus clearly context dependent but largely tumor suppressive. C/EBPβ levels are increased in cortical samples of Alzheimer's and Parkinson's disease victims at autopsy. Cell culture studies in mice and human microglia lines also find increased C/EBPβ activity associated with pathogenic inflammation and cytokine responses. Downstream analysis of genes regulated by C/EBPβ have significance in immune response, mitochondrial health, and autophagy . Molecular interference of these cellular processes have been shown to play

611-450: Is asynchronous replication during the DNA synthesis phase of the mitotic cycle. The replication of two alleles of the same gene can differ according to which parent the allele originated from. On the human chromosome 11p15, the methylated paternal H19 allele replicates early in the S phase while the hypomethylated maternal allele replicates later. Studies by Bergstrom et al. have determined that

658-431: Is essential for the growth of embryonic and extraembryonic tissues. Immediately after birth, H19 expression is downregulated in all tissues except for skeletal muscle. Studies by Tanos et al. suggest that the accumulation of H19 RNA in skeletal muscle cells is solely due to the stabilization of that RNA in the muscle cells during differentiation. In females, H19 is expressed postnatally during puberty and pregnancy in

705-617: Is expressed in the mammalian nervous system and plays a significant role in the development and function of nerve cells . C/EBPβ plays a role in neuronal differentiation, in learning, in memory processes, in glial and neuronal cell functions, and in neurotrophic factor expression. The C/EBPα , C/EBPβ , C/EBPγ and C/EBPδ genes are without introns . C/EBPζ has four exons ; C/EBPε has two, which lead to four isoforms due to an alternative use of promoters and splicing . For C/EBPα and C/EBPβ, different sizes of polypeptides can be produced by alternative use of initiation codons . This

752-421: Is expressed. The expression level of H19 RNA in the epithelial cells of the endometrium increases as tissue differentiation is lost in endometrial cancer. In ovarian cancers , 75% of low malignancy tumors and 65% of invasive ovarian carcinomas are H19 RNA positive. Normal breast tissue does not express H19 RNA, except during puberty and pregnancy in the mammary glands. However, in breast cancer , 72.5% of

799-428: Is found in the following cancers: adrenocortical neoplasms, choriocarcinomas, hepatocellular carcinomas, bladder cancers, ovarian serous epithelial cancers, head and neck carcinomas, endometrial cancer, breast cancer, acute T cell leukemia/lymphoma, Wilms' tumor , testicular germ cell cancer, esophageal cancer and lung cancer. Cellular DNA integrity is often compromised in cancer. Genome instability can refer to

846-645: Is only transcribed from the maternally inherited allele ; the paternal H19 allele is not expressed. H19 was first named ASM (for Adult Skeletal Muscle) because of its expression in adult skeletal muscle ("ASM") in rats. H19 is also known as BWS because aberrant H19 expression can be involved in Beckwith-Wiedemann Syndrome ("BWS"), as well as Silver-Russell syndrome . Epigenetics deregulations at H19 imprinted gene in sperm have been observed associated with male infertility . The H19 gene contains 3 Sp1 binding sites, however these 3 sites are present in

893-495: Is present in several gene promoters. They are characterized by a highly conserved basic-leucine zipper (bZIP) domain at the C-terminus . This domain is involved in dimerization and DNA binding, as are other transcription factors of the leucine zipper domain-containing family ( c-Fos and c-jun ). The bZIP domain structure of C/EBPs is composed of an α-helix that forms a "coiled coil" structure when it dimerizes. Members of

940-497: Is significantly different from that of normal adrenals and carcinoma adrenals, leading Gao et al. to suggest that site 11 is the initial methylated CpG that eventually leads to widespread methylation of the H19 promoter. Choriocarcinomas , in contrast to adrenal carcinomas, have upregulated H19 and downregulated IGF2 expression. The upregulated H19 expression, however, came from alleles that were fully methylated. Surgically removed choriocarcinomas from human patients also exhibited

987-648: Is thought to be due to weak ribosome scanning mechanisms. The mRNA of C/EBPα can transcribe into two polypeptides. For C/EBPβ, three different polypeptides are made: LAP* (38 kDa), LAP (35 kDa) and LIP (20 kDa). The most translated isoform is LAP, then LAP* and LIP. LIP can act as an inhibitor of the other C/EBPs by forming non-functional heterodimers. C/EBPβ function is regulated by multiple mechanisms, including phosphorylation , acetylation , activation, autoregulation, and repression via other transcription factors, oncogenic elements, or chemokines . C/EBPβ can interact with CREB , NF-κB , and other proteins, leading to

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1034-461: Is tightly coupled to and dependent on the absence of H19 expression. As well, the loss of H19 in adrenal cancers may be indicative of tumor suppressor activity by H19, leading Gao et al. to suggest that the loss of H19 and subsequent gain of IGF2 may be involved in adrenal cancer induction . Although Gao et al. found that there was not one CpG methylation site that was more important than the others in downregulating H19 expression, they did find that

1081-410: Is tightly linked to the ploidy of the cell. Diploid liver cells express high levels of H19, whereas the polyploid cell fraction do not express H19. Also, diploid mesenchymal stem cells express high levels of H19 compared to polyploid mesenchymal stem cells. Knock-down of H19 lead to increased polyploidization of mesenchymal stem cells, and induced polyploidy resulted in reduced expression of H19, providing

1128-707: The C/EBP family can form homodimers or heterodimers with other C/EBPs and with other transcription factors, which may or may not contain the leucine zipper domain. The dimerization is necessary to enable C/EBPs to bind specifically to DNA through a palindromic sequence in the major groove of the DNA. C/EBP proteins also contain activation domains at the N-terminus and regulatory domains. These proteins are found in hepatocytes , adipocytes , hematopoietic cells , spleen , kidney , brain , and many other organs. C/EBP proteins are involved in different cellular responses, such as in

1175-452: The H19 loci were observed. Verhaugh et al. investigated various polymorphisms in the H19 gene and found that some heterozygous SNP polymorphisms, such as rs2839698 TC, were associated with a decreased risk of developing non-muscle invasive bladder cancer as well as bladder cancer overall; however, this association disappeared for homozygotes (CC). In normal endometrial tissue, there is no H19 expression; however, in endometrial cancer , H19

1222-544: The Royal Navy HMS ; Harvester  (H19) , a Royal Navy H-class destroyer London Buses route H19 , a public transportation route in London, England Sikorsky H-19 , an American helicopter [REDACTED] Topics referred to by the same term This disambiguation page lists articles associated with the same title formed as a letter–number combination. If an internal link led you here, you may wish to change

1269-566: The absence of adipogenic stimuli. C/EBPβ and δ promote adipogenesis, at least in part by inducing the expression of the "master" adipogenic transcription factors C/EBPα and PPARγ . C/EBPα is required both for adipogenesis and for normal adipocyte function. For example, mice lacking C/EBPα in all tissues except the liver (where it is needed to avoid postnatal lethality) show abnormal adipose tissue formation. Moreover, ectopic expression of C/EBPα in various fibroblast cell lines promotes adipogenesis. C/EBPα probably promotes adipogenesis by inducing

1316-405: The accumulation of extra copies of DNA/chromosomes, chromosomal translocations, chromosomal inversion, chromosome deletions, single stranded breaks in DNA, double stranded breaks in DNA, the intercalation of foreign substances into the DNA double helix, or any abnormal changes in DNA tertiary structure that can cause either the loss of DNA, or the misexpression of genes. It appears that H19 expression

1363-419: The breast adenocarcinomas studied by Adriaenssens et al. displayed increased H19 expression when compared to normal breast tissue. Of the tissues with upregulated H19, 92.2% are stromal cells and only 2.9% are epithelial cells . Studies by Berteaux et al. have also found that the overexpression of H19 in breast cancer cells promotes proliferation. The expression of H19 in these cells is also independent of

1410-508: The control of cellular proliferation, growth and differentiation, in metabolism , and in immunity . Nearly all the members of the C/EBP family can induce transcription through their activation domains by interacting with components of the basal transcription apparatus. (C/EBPγ is an exception that lacks a functional transcriptional activation domain.) Their expression is regulated at multiple levels, including through hormones , mitogens , cytokines , nutrients , and other factors. This protein

1457-510: The early stages of adipocyte differentiation ( adipogenesis ), while C/EBPα is upregulated during the terminal stages of adipogenesis. In vitro and in vivo studies have demonstrated that each plays an important role in this process. For example, Murine Embryonic Fibroblasts (MEFs) from mice lacking both C/EBPβ and C/EBPδ show impaired adipocyte differentiation in response to adipogenic stimuli. In contrast, ectopic expression of C/EBPβ and δ in 3T3-L1 preadipocytes promotes adipogenesis, even in

H19 - Misplaced Pages Continue

1504-529: The expression of PPARγ. C/EBPβ has been found to have a role in the development of osteoporosis . The full-length isoform of the C/EBPβ protein (LAP) activates the MafB gene, whereas the short isoform (LIP) suppresses it. MafB gene activation suppresses the formation of osteoclasts . Thus, upregulation of LAP diminishes the number of osteoclasts, and this weakens the osteoporotic process, whereas upregulation of LIP does

1551-450: The growth (benefit) of his offspring. However, within the same pregnancy, the mother wants to conserve as much of her resources as possible towards future births without compromising the health of the child(ren) she is currently carrying. H19 contains a differentially methylated region that is also an imprinting control region. This imprinting control region is differentially methylated at its CpGs according to parental inheritance. Usually,

1598-499: The increase in CpG methylation in adrenal carcinomas followed the pattern of methylation of the normal, hyperplasia and adenoma adrenals. The mean percent methylation of H19 CpGs peaked at sites 9 and 10 in normal, hyperplasia, adenoma and carcinoma adrenals and the lowest mean percent methylation of H19 CpGs dipped at site 7 in normal, hyperplasia, adenoma and carcinoma adrenals. The mean percent methylation of H19 CpGs at sites 13 and 14, after

1645-411: The later-replicating maternal H19 allele is CTCF-bound, and that it is this CTCF binding that determines the time of H19 replication. Evidence for the identification of H19 as an oncogene: Evidence against the identification of H19 as an oncogene: Definition of an oncofetal gene: H19, while possessing oncogenic properties, is best defined as an oncofetal RNA gene because: Increased H19 expression

1692-507: The lethality of H19 overexpression in embryonic mice: In the early placentae (6–8 weeks gestation), both parental H19 alleles (maternal and paternal) are expressed. After 10 weeks gestation and in full term placentae, there is exclusive expression of H19 from the maternal chromosome. In the embryo, maternal expression of H19 is present in endodermal and mesodermal tissues. The regulated expression of H19, from biallelic to monoallelic, throughout embryonic development suggests that regulation

1739-452: The link to point directly to the intended article. Retrieved from " https://en.wikipedia.org/w/index.php?title=H19&oldid=1085842744 " Category : Letter–number combination disambiguation pages Hidden categories: Short description is different from Wikidata All article disambiguation pages All disambiguation pages H19 (gene) 283120 n/a ENSG00000130600 ENSG00000288237 n/a n

1786-571: The loss of imprinting for the H19 promoter is a characteristic of hepatocellular carcinoma is not known, as some cell lines exhibit loss of imprinting while others did not. Bladder mucosa is one of the tissues that express high levels of H19 RNA prenatally. In bladder cancers , H19 is also upregulated and present in most stages. The presence of H19 RNA was strongest in bladder carcinomas (sampled in situ) that tend to progress rapidly to invasive cancer as well as invasive transitional cell carcinomas. In samples of bladder carcinoma, loss of imprinting at

1833-452: The mammary glands, and in the uterus during pregnancy. A study by Shoshani et al. suggests that H19 is continued to be expressed in high amounts in the liver after birth, specifically in diploid hepatocytes. Genomic imprinting is surmised to have arisen due to the conflicting interests of maternal and paternal genes within a pregnancy. Within a pregnancy, the father wants the mother to devote as much of her resources as possible towards

1880-402: The methylation of the H19 promoter reduces H19 expression. The paternal H19 allele, which is silent postnatally, shows increasing methylation of CpGs in its promoter with gestation time in the fetus. It appears conclusive that the H19 gene is epigenetically controlled via methylation, where methylation on or near the vicinity of one allele prevents the expression of that allele. As well, based on

1927-583: The opposite, increasing loss of bone mass. The LAP/LIP balance is determined by the mTOR protein. Inhibition of the expression of mTOR can stop osteoclast activity. CCAAT/enhancer-binding proteins are often involved in growth arrest and differentiation, which has been interpreted to suggest that these proteins harbor tumor suppressive activities. However, CCAAT/enhancer-binding protein over-expression correlates with poor prognosis in glioblastoma and promotes genomic instability in cervical cancer, hinting at an oncogenic role. Importantly, however, C/EBPδ acts as

H19 - Misplaced Pages Continue

1974-466: The paternal copy of H19 is methylated and silent while the maternal copy is hypomethylated or unmethylated and expressed in the offspring cell. Methylation of the H19 promoter is negatively correlated with H19 expression. As methylation of the promoter reaches 100%, H19 expression from that promoter approaches 0. At the same time as H19 expression decreases, the expression of IGF2, a neighboring gene on chromosome 11, increases. Cells treated with Azad,

2021-485: The presence of the E2F1 transcription factor. The H19 gene codes for a 2.3 kb RNA product. It is transcribed by RNA polymerase II, spliced and polyadenylated , but it does not appear to be translated. After many studies, researchers finally concluded that the end product of the H19 gene is a RNA strand for the following reasons: Loss of function and overexpression experiments on H19 have revealed two things: Mice with

2068-505: The results from Banet et al. , it appears that functional H19 imprinting occurs during early placenta development. In addition, methylation loss at H19 imprinted gene has been observed associated with MTHFR gene promoter hypermethylation in semen samples from infertile males. Similarly, the CTCF -binding site 6 region of H19 can also be hypomethylated with MTHFR gene promoter hypermethylation . A common characteristic of imprinted genes

2115-455: The transcription start site, is insignificant between normal, hyperplasia, adenoma and carcinoma adrenals. This is because methylation of CpGs after the transcription start site is assumed to interfere with RNA polymerase II during transcription. Another point of interest is the significant difference in CpG methylation at site 11 between normal and hyperplasia adrenals. The mean percent CpG methylation at site 11 for hyperplasia and adenoma adrenals

2162-673: The tumor suppressor protein p53 and the cell cycle marker Ki-67 . However, the presence of tumor suppressor protein pRb and transcription factor E2F 6 is sufficient to repress H19 expression in breast cancer cells. In experiments conducted by Doyle et al. , it was found that MCF-7, a breast adenomacarcinoma cell line, did not express the H19 gene; however a subline of MCF-7 with a multidrug resistance phenotype, MCF-7/AdrVp, had upregulation of H19. Curiously, mutant revertant MCF-7/AdrVp cells that lost their multidrug resistance and became drug-sensitive also lost H19 expression. Drug-resistant MCF-AdrVp cells do not overexpress P-glycoprotein ,

2209-424: Was more methylation of CpGs than in normal, hyperplasia and adenoma adrenals. Consequently, normal H19 expression was detectable in normal and hyperplasia adrenals, but in carcinomas and surprisingly, adenomas, there was a lower H19 expression that was coupled with detectable (increased) IGF2 expression. The presence of IGF2 RNA expression when H19 RNA was downregulated provides further evidence that IGF2 expression

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