Faculty Opinions recommendation of The role of DNA methylation in setting up chromatin structure during development.

2003 ◽  
Author(s):  
Frank Lyko
Keyword(s):  
Dna Methylation ◽  
Chromatin Structure

Retrovirus-induced interference with collagen I gene expression in Mov13 fibroblasts is maintained in the absence of DNA methylation

1991 ◽  
Vol 11 (1) ◽  
pp. 47-54
Author(s):  
H Chan ◽  
S Hartung ◽  
M Breindl
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Chromatin Structure ◽  
Transcriptional Activity ◽  
Xenopus Laevis Oocytes ◽  
Regulatory Sequences ◽  
Type I ◽  
Wild Type ◽  
Col1a1 Gene

We have studied the role of DNA methylation in repression of the murine alpha 1 type I collagen (COL1A1) gene in Mov13 fibroblasts. In Mov13 mice, a retroviral provirus has inserted into the first intron of the COL1A1 gene and blocks its expression at the level of transcriptional initiation. We found that regulatory sequences in the COL1A1 promoter region that are involved in the tissue-specific regulation of the gene are unmethylated in collagen-expressing wild-type fibroblasts and methylated in Mov13 fibroblasts, confirming and extending earlier observations. To directly assess the role of DNA methylation in the repression of COL1A1 gene transcription, we treated Mov13 fibroblasts with the demethylating agent 5-azacytidine. This treatment resulted in a demethylation of the COL1A1 regulatory sequences but failed to activate transcription of the COL1A1 gene. Moreover, the 5-azacytidine treatment induced a transcription-competent chromatin structure in the retroviral sequences but not in the COL1A1 promoter. In DNA transfection and microinjection experiments, we found that the provirus interfered with transcriptional activity of the COL1A1 promoter in Mov13 fibroblasts but not in Xenopus laevis oocytes. In contrast, the wild-type COL1A1 promoter was transcriptionally active in Mov13 fibroblasts. These experiments showed that the COL1A1 promoter is potentially transcriptionally active in the presence of proviral sequences and that Mov13 fibroblasts contain the trans-acting factors required for efficient COL1A1 gene expression. Our results indicate that the provirus insertion in Mov13 can inactivate COL1A1 gene expression at several levels. It prevents the developmentally regulated establishment of a transcription-competent methylation pattern and chromatin structure of the COL1A1 domain and, in the absence of DNA methylation, appears to suppress the COL1A1 promoter in a cell-specific manner, presumably by assuming a dominant chromatin structure that may be incompatible with transcriptional activity of flanking cellular sequences.

The role of DNA methylation in setting up chromatin structure during development

2003 ◽  
Vol 34 (2) ◽  
pp. 187-192 ◽  
Author(s):  
Tamar Hashimshony ◽  
Jianmin Zhang ◽  
Ilana Keshet ◽  
Michael Bustin ◽  
Howard Cedar
Keyword(s):  
Dna Methylation ◽  
Chromatin Structure

scholarly journals Role of the Promoter in Maintaining Transcriptionally Active Chromatin Structure and DNA Methylation Patterns In Vivo

2003 ◽  
Vol 23 (12) ◽  
pp. 4150-4161 ◽  
Author(s):  
Sung-Hae Lee Kang ◽  
Christine Mione Kiefer ◽  
Thomas P. Yang
Keyword(s):  
Dna Methylation ◽  
Chromatin Structure ◽  
Dnase I ◽  
Dnase I Hypersensitivity ◽  
Translation Start ◽  
Dnase I Sensitivity ◽  
Active Transcription ◽  
Methylation Patterns

ABSTRACT Establishment and maintenance of differential chromatin structure between transcriptionally competent and repressed genes are critical aspects of transcriptional regulation. The elements and mechanisms that mediate formation and maintenance of these chromatin states in vivo are not well understood. To examine the role of the promoter in maintaining chromatin structure and DNA methylation patterns of the transcriptionally active X-linked HPRT locus, 323 bp of the endogenous human HPRT promoter (from position −222 to +102 relative to the translation start site) was replaced by plasmid sequences by homologous recombination in cultured HT-1080 male fibrosarcoma cells. The targeted cells, which showed no detectable HPRT transcription, were then assayed for effects on DNase I hypersensitivity, general DNase I sensitivity, and DNA methylation patterns across the HPRT locus. In cells carrying the deletion, significantly diminished DNase I hypersensitivity in the 5′ flanking region was observed compared to that in parental HT-1080 cells. However, general DNase I sensitivity and DNA methylation patterns were found to be very similar in the mutated cells and in the parental cells. These findings suggest that the promoter and active transcription play a relatively limited role in maintaining transcriptionally potentiated epigenetic states.

scholarly journals Retrovirus-induced interference with collagen I gene expression in Mov13 fibroblasts is maintained in the absence of DNA methylation.

1991 ◽  
Vol 11 (1) ◽  
pp. 47-54 ◽  
Author(s):  
H Chan ◽  
S Hartung ◽  
M Breindl
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Chromatin Structure ◽  
Transcriptional Activity ◽  
Xenopus Laevis Oocytes ◽  
Regulatory Sequences ◽  
Type I ◽  
Wild Type ◽  
Col1a1 Gene

We have studied the role of DNA methylation in repression of the murine alpha 1 type I collagen (COL1A1) gene in Mov13 fibroblasts. In Mov13 mice, a retroviral provirus has inserted into the first intron of the COL1A1 gene and blocks its expression at the level of transcriptional initiation. We found that regulatory sequences in the COL1A1 promoter region that are involved in the tissue-specific regulation of the gene are unmethylated in collagen-expressing wild-type fibroblasts and methylated in Mov13 fibroblasts, confirming and extending earlier observations. To directly assess the role of DNA methylation in the repression of COL1A1 gene transcription, we treated Mov13 fibroblasts with the demethylating agent 5-azacytidine. This treatment resulted in a demethylation of the COL1A1 regulatory sequences but failed to activate transcription of the COL1A1 gene. Moreover, the 5-azacytidine treatment induced a transcription-competent chromatin structure in the retroviral sequences but not in the COL1A1 promoter. In DNA transfection and microinjection experiments, we found that the provirus interfered with transcriptional activity of the COL1A1 promoter in Mov13 fibroblasts but not in Xenopus laevis oocytes. In contrast, the wild-type COL1A1 promoter was transcriptionally active in Mov13 fibroblasts. These experiments showed that the COL1A1 promoter is potentially transcriptionally active in the presence of proviral sequences and that Mov13 fibroblasts contain the trans-acting factors required for efficient COL1A1 gene expression. Our results indicate that the provirus insertion in Mov13 can inactivate COL1A1 gene expression at several levels. It prevents the developmentally regulated establishment of a transcription-competent methylation pattern and chromatin structure of the COL1A1 domain and, in the absence of DNA methylation, appears to suppress the COL1A1 promoter in a cell-specific manner, presumably by assuming a dominant chromatin structure that may be incompatible with transcriptional activity of flanking cellular sequences.

scholarly journals Role of DNA methylation and the DNA methyltransferases in learning and memory

2014 ◽  
Vol 16 (3) ◽  
pp. 359-371 ◽  
Keyword(s):  
Dna Methylation ◽  
Learning And Memory ◽  
Chromatin Structure ◽  
Behavioral Plasticity ◽  
Dna Methyltransferases ◽  
Memory Formation ◽  
Dynamic Regulation ◽  
Current Review ◽  
The Brain

Dynamic regulation of chromatin structure in postmitotic neurons plays an important role in learning and memory. Methylation of cytosine nucleotides has historically been considered the strongest and least modifiable of epigenetic marks. Accumulating recent data suggest that rapid and dynamic methylation and demethylation of specific genes in the brain may play a fundamental role in learning, memory formation, and behavioral plasticity. The current review focuses on the emergence of data that support the role of DNA methylation and demethylation, and its molecular mediators in memory formation.

scholarly journals Impact of DNA methylation on 3D genome structure

2020 ◽  
Author(s):  
Diana Buitrago ◽  
Mireia Labrador ◽  
Juan Pablo Arcon ◽  
Rafael Lema ◽  
Oscar Flores ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Chromatin Structure ◽  
Chromatin Condensation ◽  
Genome Structure ◽  
Model System ◽  
Structure And Function ◽  
3D Genome ◽  
And Function

Abstract The extreme complexity of epigenetic regulation in higher organisms makes the determination of the intrinsic effect of DNA methylation in chromatin structure and function challenging. We investigated the role of DNA methylation in a simpler model system, budding yeast (Saccharomyces cerevisiae), an organism in which methylation-related machinery is normally absent thus making it a perfect model system to study the intrinsic role of methylation in chromatin structure and function. With this aim, we expressed the murine DNA Methyl Transferases in S. cerevisiae and analyzed the correlation between DNA methylation, nucleosome positioning, gene expression and 3D genome organization. We showed that despite the lack of machinery for positioning and reading of methylation marks, the methylation pattern follows a conserved pattern, the level of DNA methylation being very low at the 5’ end of the gene, and then increasing gradually toward the 3’ end, mimicking mammalian behavior. DNA methylation and gene expression correlate as DNA methylation is lower at the TSS and higher at the TTS in highly expressed genes compared to lowly expressed ones, mimicking again mammalian behavior. We found that methylated DNA is unlikely to be wrapped around nucleosomes, but is concentrated in linkers and nucleosome free regions. DNA methylation increases chromatin condensation in the peri-centromeric region, decreases overall DNA flexibility and favors the heterochromatin state. Taken together, these results demonstrate that methylation intrinsically modulates chromatin structure and function even in the absence of cellular machinery evolved to recognize and process the methylation signal.

DNA methylation in satellite repeats disorders

2019 ◽  
Vol 63 (6) ◽  
pp. 757-771 ◽  
Author(s):  
Claire Francastel ◽  
Frédérique Magdinier
Keyword(s):  
Dna Methylation ◽  
Human Genome ◽  
Repetitive Dna ◽  
Dna Sequences ◽  
Satellite Repeats ◽  
Tremendous Progress ◽  
Genes Encoding ◽  
Dna Elements ◽  
Near Future

Abstract Despite the tremendous progress made in recent years in assembling the human genome, tandemly repeated DNA elements remain poorly characterized. These sequences account for the vast majority of methylated sites in the human genome and their methylated state is necessary for this repetitive DNA to function properly and to maintain genome integrity. Furthermore, recent advances highlight the emerging role of these sequences in regulating the functions of the human genome and its variability during evolution, among individuals, or in disease susceptibility. In addition, a number of inherited rare diseases are directly linked to the alteration of some of these repetitive DNA sequences, either through changes in the organization or size of the tandem repeat arrays or through mutations in genes encoding chromatin modifiers involved in the epigenetic regulation of these elements. Although largely overlooked so far in the functional annotation of the human genome, satellite elements play key roles in its architectural and topological organization. This includes functions as boundary elements delimitating functional domains or assembly of repressive nuclear compartments, with local or distal impact on gene expression. Thus, the consideration of satellite repeats organization and their associated epigenetic landmarks, including DNA methylation (DNAme), will become unavoidable in the near future to fully decipher human phenotypes and associated diseases.

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