Although many of the questions raised by discovery imprinting have been answered, we not yet accounted for tissue- or stage-specific imprinting. The Kcnq1 imprinted domain exhibits complex tissue-specific expression patterns co-existing with a domain-wide cis-acting control element. Transcription paternally expressed antisense non-coding RNA Kcnq1ot1 silences some neighboring genes in embryo, while others are unaffected. is early cardiac development but becomes biallelic after midgestation....

Imprinting at the H19/Igf2 locus depends on a differentially methylated domain (DMD) acting as maternal-specific, methylation-sensitive insulator and paternal-specific of hypermethylation. Four repeats in DMD bind CTCF maternal allele have been proposed to recruit methylation paternal allele. We deleted four assayed effects mutation endogenous locus. The H19DMD-ΔR can successfully acquire during spermatogenesis silence H19, indicating that these functions are independent binding sites....

Pre-implantation embryos exhibit sexual dimorphisms in both primates and rodents. To determine whether these differences reflected sex-biased expression patterns, we generated transcriptome profiles for six 40,XX, 40,XY, two 39,X mouse embryonic stem (ES) cells by RNA sequencing.We found hundreds of coding non-coding RNAs that were differentially expressed between male female cells. Surprisingly, the majority autosomal included encoding transcription epigenetic chromatin remodeling factors....

Gadd45a (growth arrest and DNA-damage-inducible protein 45 alpha) plays a pivotal role in cellular stress responses is implicated DNA repair, cell cycle apoptosis.(1) Recently, it was proposed that GADD45A key regulator of active demethylation by way its repair.(2) Barreto et al. reported overexpression activated transcription from methylation-silenced reporter plasmids promoted global demethylation. siRNA-mediated knockdown levels resulted increased methylation at specific endogenous loci....

TET1 oxidizes methylated cytosine into 5-hydroxymethylcytosine (5hmC), resulting in regulation of DNA methylation and gene expression. Full length (TET1FL) has a CXXC domain that binds to unmethylated CpG islands (CGIs). This allows protect CGIs from aberrant methylation, but it also limits its ability regulate genes outside CGIs. Here, we report novel isoform (TET1ALT) unique transcription start site an alternate promoter intron 2, yielding protein with translation site. Importantly,...

Insight into how the mammalian genome is structured in vivo key to understanding transcriptional regulation. This especially true complex domains which genes are coordinately regulated by long-range interactions between cis -regulatory elements. The regulation of H19 / Igf2 imprinted region depends on presence several -acting sequences, including a methylation-sensitive insulator and shared enhancers downstream . Each parental allele has distinct expression pattern. We used chromosome...

Expression patterns between males and females vary in every adult tissue, even organs with no conspicuous dimorphisms such as the heart. While studies of male female differences have traditionally focused on influence sex hormones, these do not account for all at molecular epigenetic levels. We previously reported that a substantial number genes were differentially expressed mouse embryonic stem (ES) cells revealed dose-dependent enhancer activity response to Prdm14, key pluripotency factor...

The imprinted Kcnq1 domain contains a differentially methylated region (KvDMR) in intron 11 of Kcnq1. Kcnq1ot1 non-coding RNA emerges from the unmethylated paternal KvDMR antisense direction, resulting cis-repression neighboring genes. encompasses promoter, CTCF sites and other DNA elements, whose individual contribution to regulation endogenous is unknown. We find that inheritance deletion minimal promoter derepresses upstream Cdkn1c gene. Surprisingly, transcripts continue emerge...

The Rac-GEF P-REX1 is a key mediator of ErbB signaling in breast cancer recently implicated mammary tumorigenesis and metastatic dissemination. Although essentially undetectable normal human epithelial tissue, this markedly upregulated carcinomas, particularly the luminal subtype. mechanisms underlying upregulation are unknown. Toward goal dissecting mechanistic basis overexpression cancer, study we focused on analysis methylation PREX1 gene promoter.To determine status promoter region, used...

Abstract Background Gene regulation in eukaryotes is a complex process entailing the establishment of transcriptionally silent chromatin domains interspersed with regions active transcription. Imprinted consist clusters genes, some which exhibit parent-of-origin dependent monoallelic expression, while others are biallelic. The Kcnq1 imprinted domain illustrates complexities long-range that coexists local exceptions. A paternally expressed repressive non-coding RNA, Kcnq1ot1 , regulates up to...

DNA methylation, chromatin-binding proteins, and looping are common components regulating genomic imprinting which leads to parent-specific monoallelic gene expression. Loss of methylation (LOM) at the human center 2 (IC2) on chromosome 11p15 is most cause overgrowth disorder Beckwith-Wiedemann Syndrome (BWS). Here, we report a familial transmission 7.6 kB deletion that ablates core promoter KCNQ1. This structural alteration IC2 LOM causes recurrent BWS. We find occupancy chromatin organizer...

Abstract Background Mammalian gonadal sex is determined by the presence or absence of a Y chromosome and subsequent production hormones contributes to secondary sexual differentiation. However, chromosome-linked genes encoding dosage-sensitive transcription epigenetic factors are expressed well before gonad formation have potential establish sex-biased expression that persists beyond appearance hormones. Here, we apply comparative bioinformatics analysis on pair published single-cell...

Common protein motifs between histidine decarboxylase (HDC) and ornithine (ODC) were detected by computational analysis. Mutants generated expressed in vitro. In both enzymes, terminal PEST-region-containing fragments are not essential for decarboxylation (PEST regions sequence enriched proline, glutamic acid, serine threonine residues a hydrophilic fragment flanked cationic amino acids). The substitution of very well conserved residue alanine causes severalfold increase the apparent Km...

Thymidine incorporation into the DNA of anterior pituitary gland is stimulated by estrogen. We studied relationship between this effect and expression protooncogenes c-myc c-fos. Within one hour after estrogen administration, level c-fos mRNA increased in remained high throughout experimental period (16 to 22 hrs). Transcription prolactin gene, targets action, was at same time intervals. There were no modifications growth hormone level. Thus, induced an early period.

Prader-Willi (PWS) and Angelman (AS) are syndromes of developmental impairment that result from the loss expression imprinted genes in paternal or maternal 15q11-q13 chromosome. Diagnosis on a clinical basis is difficult newborns young infants; thus, suitable molecular test capable revealing chromosomal abnormalities required. We used variety cytogenetic approaches, such as, chromosome G banding, fluorescent situ hybridization, DNA methylation test, set 15 polymorphisms to characterize...