Identification of the Physiological Promoter for Spinocerebellar Ataxia 2 Gene Reveals a CpG Island for Promoter Activity Situated into the Exon 1 of This Gene and Provides Data about the Origin of the Nonmethylated State of These Types of Islands

1999 ◽  
Vol 254 (2) ◽  
pp. 315-318 ◽  
Author(s):  
Jorge Aguiar ◽  
Simon Santurlidis ◽  
Joachim Nowok ◽  
Christiane Alexander ◽  
Doda Rudnicki ◽  
...  
Keyword(s):  
Spinocerebellar Ataxia ◽  
Promoter Activity ◽  
Cpg Island ◽  
Exon 1 ◽  
Spinocerebellar Ataxia 2

scholarly journals 5′-Heterogeneity of Glucocorticoid Receptor Messenger RNA Is Tissue Specific: Differential Regulation of Variant Transcripts by Early-Life Events

2000 ◽  
Vol 14 (4) ◽  
pp. 506-517 ◽  
Author(s):  
J. A. McCormick ◽  
V. Lyons ◽  
M. D. Jacobson ◽  
J. Noble ◽  
J. Diorio ◽  
...  
Keyword(s):  
Glucocorticoid Receptor ◽  
Stress Responses ◽  
Early Life ◽  
Messenger Rna ◽  
Promoter Activity ◽  
Cpg Island ◽  
Rnase Protection ◽  
Exon 2 ◽  
Tissue Specific ◽  
Exon 1

Abstract Glucocorticoid receptor (GR) gene expression is regulated in a complex tissue-specific manner, notably by early-life environmental events that program tissue GR levels. We have identified and characterized several new rat GR mRNAs. All encode a common protein, but differ in their 5′-leader sequences as a consequence of alternate splicing of, potentially, 11 different exon 1 sequences. Most are located in a 3-kb CpG island, upstream of exon 2, that exhibits substantial promoter activity in transfected cells. Ribonuclease (RNase) protection analysis demonstrated significant levels of six alternate exons 1 in vivo in rat, with differences between liver, hippocampus, and thymus reflecting tissue-specific differences in promoter activity. Two of the alternate exons 1 (exons 16 and 110) were expressed in all tissues examined, together present in 77–87% of total GR mRNA. The remaining GR transcripts contained tissue-specific alternate first exons. Importantly, tissue-specific first exon usage was altered by perinatal environmental manipulations. Postnatal handling, which permanently increases GR in the hippocampus, causing attenuation of stress responses, selectively elevated GR mRNA containing the hippocampus-specific exon 17. Prenatal glucocorticoid exposure, which increases hepatic GR expression and produces adult hyperglycemia, decreased the proportion of hepatic GR mRNA containing the predomin-ant exon 110, suggesting an increase in a minor exon 1 variant. Such tissue specificity of promoter usage allows differential GR regulation and programming.

scholarly journals DNA Methylation of Human Choline Kinase Alpha Promoter-Associated CpG Islands in MCF-7 Cells

Genes ◽  
2021 ◽  
Vol 12 (6) ◽  
pp. 853
Author(s):  
Siti Aisyah Faten Mohamed Sa’dom ◽  
Sweta Raikundalia ◽  
Shaharum Shamsuddin ◽  
Wei Cun See Too ◽  
Ling Ling Few
Keyword(s):  
Dna Methylation ◽  
Transcription Factor ◽  
Binding Site ◽  
Promoter Activity ◽  
Cytosine Methylation ◽  
Cpg Island ◽  
Cpg Islands ◽  
Site Directed Mutagenesis ◽  
Choline Kinase ◽  
Mcf 7

Choline kinase (CK) is the enzyme catalyzing the first reaction in CDP-choline pathway for the biosynthesis of phosphatidylcholine. Higher expression of the α isozyme of CK has been implicated in carcinogenesis, and inhibition or downregulation of CKα (CHKA) is a promising anticancer approach. This study aimed to investigate the regulation of CKα expression by DNA methylation of the CpG islands found on the promoter of this gene in MCF-7 cells. Four CpG islands have been predicted in the 2000 bp promoter region of ckα (chka) gene. Six CpG island deletion mutants were constructed using PCR site-directed mutagenesis method and cloned into pGL4.10 vectors for promoter activity assays. Deletion of CpG4C region located between –225 and –56 significantly increased the promoter activity by 4-fold, indicating the presence of important repressive transcription factor binding site. The promoter activity of methylated full-length promoter was significantly lower than the methylated CpG4C deletion mutant by 16-fold. The results show that DNA methylation of CpG4C promotes the binding of the transcription factor that suppresses the promoter activity. Electrophoretic mobility shift assay analysis showed that cytosine methylation at MZF1 binding site in CpG4C increased the binding of putative MZF1 in nuclear extract. In conclusion, the results suggest that DNA methylation decreased the promoter activity by promoting the binding of putative MZF1 transcription factor at CpG4C region of the ckα gene promoter.

scholarly journals Ikaros Is Regulated through Multiple Histone Modifications and Deoxyribonucleic Acid Methylation in the Pituitary

2007 ◽  
Vol 21 (5) ◽  
pp. 1205-1215 ◽  
Author(s):  
Xuegong Zhu ◽  
Sylvia L. Asa ◽  
Shereen Ezzat
Keyword(s):  
Dna Methylation ◽  
Histone Modifications ◽  
Cpg Island ◽  
Chromatin Accessibility ◽  
Dominant Negative ◽  
Nurd Complex ◽  
Human Pituitary ◽  
Untranslated Exon ◽  
Exon 1 ◽  
Mouse Pituitary

Abstract The transcription factor Ikaros (Ik) is at the center of a functionally diverse chromatin-remodeling network that is critical for the development and regulation of both the immune and endocrine systems. Dominant negative forms of Ik result in neoplastic growth in mouse genetic studies and have been identified in human tumors. Ik modulates chromatin accessibility through associations with members of the NURD complex including histone deacetylase complexes. We show here that Ik expression in mouse pituitary corticotroph cells is itself regulated through histone modifications as well as DNA methylation. Examination of primary human pituitary specimens also identified a correlation of loss of Ik expression with the presence of DNA methylation in the untranslated exon 1 CpG island. These findings have important implications for the understanding of Ikaros’ role in epigenetic functions and suggest a potential role for demethylating agents in the treatment of related disorders.

Birth after pre-implantation genetic diagnosis (PGD) of spinocerebellar ataxia 2 (Sca2)

2008 ◽  
Vol 28 (2) ◽  
pp. 126-130 ◽  
Author(s):  
Céline Moutou ◽  
Jean-Christophe Nicod ◽  
Nathalie Gardes ◽  
Stéphane Viville
Keyword(s):  
Spinocerebellar Ataxia ◽  
Genetic Diagnosis ◽  
Spinocerebellar Ataxia 2

Supratentorial and infratentorial damage in spinocerebellar ataxia 2: A diffusion-weighted MRI study

2013 ◽  
Vol 29 (6) ◽  
pp. 780-786 ◽  
Author(s):  
Elena Salvatore ◽  
Enrico Tedeschi ◽  
Carmine Mollica ◽  
Caterina Vicidomini ◽  
Andrea Varrone ◽  
...  
Keyword(s):  
Spinocerebellar Ataxia ◽  
Diffusion Weighted Mri ◽  
Diffusion Weighted ◽  
Mri Study ◽  
Spinocerebellar Ataxia 2

scholarly journals Functional analysis of the promoter region of the human phosphotyrosine phosphatase activator gene: Yin Yang 1 is essential for core promoter activity

1999 ◽  
Vol 344 (3) ◽  
pp. 755-763 ◽  
Author(s):  
Veerle JANSSENS ◽  
Christine VAN HOOF ◽  
Ivo DE BAERE ◽  
Wilfried MERLEVEDE ◽  
Jozef GORIS
Keyword(s):  
Binding Sites ◽  
Promoter Region ◽  
Promoter Activity ◽  
Cpg Island ◽  
Luciferase Reporter ◽  
Binding Motif ◽  
Phosphotyrosine Phosphatase ◽  
Yin Yang 1 ◽  
Yin Yang

The phosphotyrosine phosphatase activator (PTPA) has been isolated as an in vitro regulator of protein phosphatase 2A. Human PTPA is encoded by a single gene, the structure and chromosomal localization of which have been determined in our previous work. Here we describe the further isolation, sequencing and functional characterization of the PTPA promoter region. In agreement with its ubiquitous expression, the PTPA promoter displays several characteristics of housekeeping genes: it lacks both a TATA-box and a CAAT-box, it is very GC-rich and it contains an unmethylated CpG island surrounding the transcription initiation site. Transient transfection experiments in different cell types with several truncated chimaeric luciferase reporter gene plasmids revealed the importance of the region between positions -67 and -39 for basal promoter activity. This region coincides remarkably well with the determined CpG island. Further analysis of this region demonstrated the presence of a Yin Yang 1 (YY1) binding motif at positions -52 to -44. Binding of YY1 to this sequence is demonstrated in bandshift and DNase I footprinting experiments. Another YY1 binding motif is found in the 5ʹ untranslated region, at positions +27 to +35. Mutations in either of these sites, abolishing YY1 binding in vitro, have differential effects on promoter activity. Point mutations in both sites completely abolish promoter activity. Moreover, induction of promoter activity by co-transfection with a YY1 expression plasmid is fully dependent upon the presence of both intact YY1 binding sites. Thus YY1 apparently mediates basal transcription of the human PTPA gene through two binding sites within its proximal promoter.

Infantile Onset Spinocerebellar Ataxia 2 (SCA2)

2013 ◽  
Vol 29 (1) ◽  
pp. 139-144 ◽  
Author(s):  
Ankur Singh ◽  
Mohammed Faruq ◽  
Mitali Mukerji ◽  
Manish Kumar Dwivedi ◽  
Sumit Pruthi ◽  
...  
Keyword(s):  
Spinocerebellar Ataxia ◽  
Spinocerebellar Ataxia 2

scholarly journals Hypomethylation of Monoamine Oxidase A promoter/exon 1 region is associated with temper outbursts in Prader-Willi syndrome

2021 ◽  
Author(s):  
Maximilian Deest ◽  
Vanessa Buchholz ◽  
Kirsten Jahn ◽  
Christian Eberlein ◽  
Stefan Bleich ◽  
...  
Keyword(s):  
Monoamine Oxidase ◽  
Physical Aggression ◽  
Crucial Role ◽  
Cpg Island ◽  
Monoamine Oxidase A ◽  
Prader Willi Syndrome ◽  
Behavioural Phenotype ◽  
Methylation Rate ◽  
Exon 1 ◽  
Temper Outbursts

Background: Prader-Willi syndrome (PWS) is a rare neurodevelopmental disorder caused by the absence of paternally expressed and maternally imprinted genes on chromosome 15q 11.2-13. It is associated with a certain behavioural phenotype with repetitive and ritualistic behaviours, skin-picking and temper outbursts. Temper outbursts are characterized by verbal and physical aggression with screaming, destroying property, and/or physical aggression towards others. They drastically effect the quality of life of the individuals as well as the relatives and caregivers. Recent studies show a promising therapeutic effect of serotonin reuptake inhibitors like sertraline on frequency and intensity of outbursts. Monoamine oxidase A (MAOA) (X p11.23) plays a crucial role in the metabolism of monoamines such as serotonin, norepinephrine, and dopamine. Dysregulation in methylation of the CpG island spanning the promoter region and exon 1 of MAOA is implicated in impulsive and aggressive behaviour. Methods: In the present study, methylation rates of CpG dinucleotides in the MAOA promoter and exon 1 region were determined from DNA derived from whole blood samples of PWS patients (n=32) and controls (n=14) matched for age, sex and BMI via bisulfite sequencing. PWS patients were grouped into those showing temper outbursts, and those who do not. Results: Overall, PWS patients show a significant lower methylation rate at the promoter/exon 1 region than healthy controls in both sexes. Furthermore, PWS patients, male as well female with temper outbursts show a significant lower methylation rate than those without temper outbursts (p<0.001 and p=0.006) Conclusion: The MAOA promoter/exon 1 region methylation seems to be dysregulated in PWS patients in sense of a hypomethylation, especially in those suffering from temper outbursts. As MAOA is involved in the metabolism of serotonin, we conclude that this dysregulation plays a crucial role in the pathophysiology of temper outbursts in PWS. Furthermore, our findings suggest, that dysregulation of certain genes outside the PWS locus contribute to the behavioural phenotype of PWS.

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