Abstract:
:ARHI has been identified as a maternally imprinted tumor suppressor gene that maps to chromosome 1p31 and whose expression is markedly down-regulated in breast cancer. To explore possible mechanisms that could silence ARHI expression, we have tested the importance of DNA methylation, histone acetylation and histone methylation in regulating ARHI expression. We found that treatment with CpG demethylating agents and/or histone deacetylase inhibitors could reactivate both the silenced and the imprinted alleles of this tumor suppressor gene. Reactivation of ARHI expression by these reagents is related to the methylation status of the CpG islands in the ARHI promoter, especially CpG island II. Chromatin immunoprecipitation assays revealed that histone H3 lysine 9/18 acetylation levels associated with ARHI in normal cells were significantly higher than those in breast cancer cell lines that lacked ARHI expression. Treatment with a CpG demethylating agent and/or histone deacetylase inhibitor could increase ARHI expression in breast cancer cells, with a corresponding increase in histone H3 lysine 9/18 acetylation and decrease in histone H3 lysine 9 methylation.
journal_name
Hum Mol Genetjournal_title
Human molecular geneticsauthors
Fujii S,Luo RZ,Yuan J,Kadota M,Oshimura M,Dent SR,Kondo Y,Issa JP,Bast RC Jr,Yu Ydoi
10.1093/hmg/ddg204subject
Has Abstractpub_date
2003-08-01 00:00:00pages
1791-800issue
15eissn
0964-6906issn
1460-2083journal_volume
12pub_type
杂志文章abstract::Retinitis pigmentosa (RP), a genetically heterogeneous group of retinopathies that occur in both non-syndromic and syndromic forms, is caused by mutations in ∼100 genes. Although recent advances in next-generation sequencing have aided in the discovery of novel RP genes, a number of the underlying contributing genes a...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddu291
更新日期:2014-11-01 00:00:00
abstract::'Pure' familial spastic paraplegias (FSP) are neurodegenerative disorders that are clinically characterized by progressive spasticity of the lower limbs and are inherited as autosomal dominant (DFSP) or autosomal recessive (RFSP) traits. The primary defect in FSP is unknown. Genetic linkage analysis was applied to fiv...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/3.8.1263
更新日期:1994-08-01 00:00:00
abstract::Rett syndrome (RTT), an X-linked postnatal disorder, results from mutations in Methyl CpG-binding protein 2 (MECP2). Survival and breathing in Mecp2(NULL/Y) animals are improved by an N-terminal tripeptide of insulin-like growth factor I (IGF-I) treatment. We determined that Mecp2(NULL/Y) animals also have a metabolic...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddt111
更新日期:2013-07-01 00:00:00
abstract::Beckwith-Wiedemann syndrome (BWS) is an overgrowth malformation syndrome that maps to human chromosome 11p15.5, a region that harbours a number of imprinted genes. We studied the methylation status of H19 and KCNQ1OT1 (LIT1/KvDMR1) in a large series of BWS patients. Different patient groups were identified: group I pa...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/10.5.467
更新日期:2001-03-01 00:00:00
abstract::The intraflagellar transport (IFT) machinery containing the IFT-A and IFT-B complexes mediates ciliary protein trafficking. Mutations in the genes encoding the six subunits of the IFT-A complex (IFT43, IFT121, IFT122, IFT139, IFT140, and IFT144) are known to cause skeletal ciliopathies, including cranioectodermal dysp...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddx421
更新日期:2018-02-01 00:00:00
abstract::The IL12B gene encodes the common p40 subunit of IL-12 and IL-23, cytokines with key roles in Th1 and Th17 biology, respectively, and genetic variation in this region significantly influences risk of psoriasis. Here, we demonstrate that a psoriasis-associated risk haplotype at the IL12B locus leads to increased expres...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddt034
更新日期:2013-05-01 00:00:00
abstract::Most quantitative trait loci (QTL) studies have focused on detecting the genetic effects of individual QTLs. This study thoroughly dissected the genetic components of type 2 diabetic mice, including a search for epistatic interactions and multi-locus additive effects that result in variation in diabetes-related phenot...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddi433
更新日期:2006-01-01 00:00:00
abstract::Meiotic recombination is of fundamental importance in creating haplotype diversity in the human genome and has the potential to cause genomic rearrangements by ectopic recombination between repeat sequences and through other changes triggered by recombination-initiating events. However, the relationship between alleli...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddl025
更新日期:2006-04-01 00:00:00
abstract::The mutation causing myotonic dystrophy (DM) has recently been identified as an unstable CTG trinucleotide repeat located in the 3' untranslated region of a gene encoding for a protein with putative serine-threonine protein kinase activity. In this report we present the genomic sequences of the human and murine DM kin...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/2.3.299
更新日期:1993-03-01 00:00:00
abstract::Oxidative stress is a prominent feature of Huntington disease (HD), and we have shown previously that reduced levels of hace1 (HECT domain and Ankyrin repeat containing E3 ubiquitin protein ligase 1) in patient striatum may contribute to the pathogenesis of HD. Hace1 promotes the stability of Nrf2 and thus plays an im...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddx394
更新日期:2018-01-15 00:00:00
abstract::Genome-wide association studies (GWAS) have identified several common loci contributing to non-obstructive azoospermia (NOA). However, a substantial fraction of NOA heritability remains undefined, especially those low-frequency [defined here as having a minor allele frequency (MAF) between 0.5 and 5%] and rare (MAF be...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddv257
更新日期:2015-10-01 00:00:00
abstract::We have identified a rare mutation (T-45C) in the low density lipoprotein (LDL)-receptor gene in a Welsh patient with a clinical diagnosis of heterozygous familial hypercholesterolaemia (FH). The mutation is in the proximal Sp1 binding site in repeat 3 of the 42 bp region of the promoter required for sterol-dependent ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/4.11.2125
更新日期:1995-11-01 00:00:00
abstract::p53 is one of the most important known tumor suppressor genes, and it is inactivated in approximately half of human cancers. p53 family members execute various functions, such as apoptosis induction and cell cycle arrest, by modulating transcriptional regulation. Therefore, the direct transcriptional targets of the p5...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddt673
更新日期:2014-06-01 00:00:00
abstract::Clinical, electrophysiological and genetic linkage studies were performed on a large autosomal dominant family with Charcot-Marie-Tooth axonal neuropathy type 2 (CMT2) with 38 members of which 14 were affected. Onset of the disease was between 16 and 30 years of age with weakness and atrophy of the hands more severe t...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/5.9.1373
更新日期:1996-09-01 00:00:00
abstract::We have explored the National Center for Biotechnology Information (NCBI) single nucleotide polymorphisms (SNPs) database for a correlation between the density of putative SNPs, as well as SNPs that map to different chromosomal locations (ambiguously mapped SNPs), and segmental duplications of DNA in chromosome region...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/11.17.1987
更新日期:2002-08-15 00:00:00
abstract::Mutations in human mitochondrial tRNA genes are associated with a number of multisystemic disorders. Using an assay that combines tRNA oxidation and circularization we have determined the relative amounts and states of aminoacylation of mutant and wild-type tRNAs in tissue samples from patients with MELAS syndrome (mi...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/9.4.467
更新日期:2000-03-01 00:00:00
abstract::DNA replication is a critical step for cells because of the propensity of replication forks to stall, as a consequence either of endogenous DNA damage or of the propensity of repeated sequences to form tertiary structures, which can impede fork progression. Moreover, as a result of stalled replication fork processing,...
journal_title:Human molecular genetics
pub_type: 杂志文章,评审
doi:10.1093/hmg/11.20.2447
更新日期:2002-10-01 00:00:00
abstract::Renal-coloboma syndrome, also known as papillorenal syndrome, is an autosomal dominant human disorder in which optic disc coloboma is associated with kidney abnormalities. Mutations in the paired domain transcription factor PAX2 have been found to be the underlying cause of this disease. Disease severity varies betwee...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddq457
更新日期:2011-01-15 00:00:00
abstract::Primary aldosteronism (PA, autonomous aldosterone production from the adrenal cortex) causes the most common form of secondary arterial hypertension (HT), which is also the most common curable form of HT. Recent studies have highlighted an important role of mutations in genes encoding potassium channels in the pathoge...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/dds333
更新日期:2012-11-15 00:00:00
abstract::Down syndrome (DS) is the most common genetic cause of mental retardation and affects many aspects of brain development. DS individuals exhibit an overall reduction in brain size with a disproportionately greater reduction in cerebellar volume. The Ts65Dn mouse is segmentally trisomic for the distal 12-15 Mb of mouse ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/9.2.195
更新日期:2000-01-22 00:00:00
abstract::Choroideremia (CHM) is an X-linked progressive eye disorder which results from defects in the human Rab escort protein-1 (REP-1) gene. A gene targeting approach was used to disrupt the mouse chm/rep-1 gene. Chimeric males transmitted the mutated gene to their carrier daughters but, surprisingly, these heterozygous fem...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/6.6.851
更新日期:1997-06-01 00:00:00
abstract::Neonatal dried blood spots (NDBS) are a widely banked sample source that enables retrospective investigation into early life molecular events. Here, we performed low-pass whole genome bisulfite sequencing (WGBS) of 86 NDBS DNA to examine early life Down syndrome (DS) DNA methylation profiles. DS represents an example ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddaa218
更新日期:2021-01-06 00:00:00
abstract::Changes to islet cell identity in response to type 2 diabetes (T2D) have been reported in rodent models, but are less well characterized in humans. We assessed the effects of aspects of the diabetic microenvironment on hormone staining, total gene expression, splicing regulation and the alternative splicing patterns o...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddz094
更新日期:2019-08-15 00:00:00
abstract::Biallelic loss-of-function mutations in the RNA-binding protein EIF4A3 cause Richieri-Costa-Pereira syndrome (RCPS), an autosomal recessive condition mainly characterized by craniofacial and limb malformations. However, the pathogenic cellular mechanisms responsible for this syndrome are entirely unknown. Here, we use...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddx078
更新日期:2017-06-15 00:00:00
abstract::Epilepsy, deafness, onychodystrophy, osteodystrophy and intellectual disability are associated with a spectrum of mutations of human TBC1D24. The mechanisms underlying TBC1D24-associated disorders and the functions of TBC1D24 are not well understood. Using CRISPR-Cas9 genome editing, we engineered a mouse with a prema...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddy445
更新日期:2019-05-01 00:00:00
abstract::Mucolipidosis IV (MLIV) is an orphan neurodevelopmental disease that causes severe neurologic dysfunction and loss of vision. Currently there is no therapy for MLIV. It is caused by loss of function of the lysosomal channel mucolipin-1, also known as TRPML1. Knockout of the Mcoln1 gene in a mouse model mirrors clinica...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddy182
更新日期:2018-08-01 00:00:00
abstract::Craniosynostosis, the abnormal development of the calvarial sutures, occurs as an autosomal dominant trait in many clinically distinct syndromes. We performed linkage analysis of a provisionally novel type of autosomal dominant craniosynostosis in a large three generational family. Linkage was established between the ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/2.2.119
更新日期:1993-02-01 00:00:00
abstract::The cone photoreceptor cyclic nucleotide-gated (CNG) channel is essential for central and color vision and visual acuity. Mutations in the channel subunits CNGA3 and CNGB3 are associated with achromatopsia and cone dystrophy. We investigated the gene expression profiles in mouse retina with CNG channel deficiency usin...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddt245
更新日期:2013-10-01 00:00:00
abstract::Over the past decades the search for disease causing variants has been focusing exclusively on the coding genome. This highly selective approach has been extremely successful resulting in the identification of thousands of disease genes, but ignores the functional and therefore disease relevance of the rest of the gen...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddw205
更新日期:2016-10-01 00:00:00
abstract::Primary open-angle glaucoma (POAG) is a complex disease with unknown causes. However, in the past decade, POAG has been linked to six chromosomal regions, of which the gene MYOC encoding myocilin and the gene OPTN encoding optineurin have been identified to harbor causal mutations (disease-causing variants, DCV). POAG...
journal_title:Human molecular genetics
pub_type: 杂志文章,评审
doi:10.1093/hmg/ddh074
更新日期:2004-04-01 00:00:00