scholarly journals DNA Methylation and Chromatin: Role(s) of Methyl-CpG-Binding Protein ZBTB38

2018 ◽  
Vol 11 ◽  
pp. 251686571881111 ◽  
Author(s):  
Maud de Dieuleveult ◽  
Benoit Miotto
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Transcription Factors ◽  
Dna Sequences ◽  
Mammalian Cells ◽  
Expression Patterns ◽  
Control Of Gene Expression ◽  
Methylated Dna

DNA methylation plays an essential role in the control of gene expression during early stages of development as well as in disease. Although many transcription factors are sensitive to this modification of the DNA, we still do not clearly understand how it contributes to the establishment of proper gene expression patterns. We discuss here the recent findings regarding the biological and molecular function(s) of the transcription factor ZBTB38 that binds methylated DNA sequences in vitro and in cells. We speculate how these findings may help understand the role of DNA methylation and DNA methylation–sensitive transcription factors in mammalian cells.

DNA methylation and epigenetic inheritance

1990 ◽  
Vol 326 (1235) ◽  
pp. 329-338 ◽  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Dna Sequences ◽  
Mammalian Cells ◽  
Germ Line ◽  
Experimental System ◽  
Epigenetic Inheritance ◽  
Epigenetic Mechanisms ◽  
Control Of Gene Expression ◽  
Developmental Programme

Classical genetics has revealed the mechanisms for the transmission of genes from generation to generation, but the strategy of the genes in unfolding the developmental programme remains obscure. Epigenetics comprises the study of the mechanisms that impart temporal and spatial control on the activities of all those genes required for the development of a complex organism from the zygote to the adult. Epigenetic changes in gene activity can be studied in relation to DNA methylation in cultured mammalian cells and it is also possible to isolate and characterize mutants with altered DNA methylase activity. Although this experimental system is quite far removed from the epigenetic controls acting during development it does provide the means to clarify the rules governing the silencing of genes by specific DNA methylation and their reactivation by demethylation. This in turn will facilitate studies on the control of gene expression in somatic cells of the developing organism or the adult. The general principles of epigenetic mechanisms can be defined. There are extreme contrasts between instability or switches in gene expression, such as those in stem-line cells, and the stable heritability of a specialized pattern of gene activities. In some situations cell lineages are known to be important, whereas in others coordinated changes in groups of cells have been demonstrated. Control of numbers of cell divisions and the size of organisms, or parts of organisms, is also essential. The epigenetic determination of gene expression can be reversed or reprogrammed in the germ line. The extent to which methylation or demethylation of specific DNA sequences can help explain these basic epigenetic mechanisms is briefly reviewed.

Control of gene expression by CpG island methylation in normal cells

2004 ◽  
Vol 32 (6) ◽  
pp. 913-915 ◽  
Author(s):  
G. Strathdee ◽  
A. Sim ◽  
R. Brown
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Cpg Island ◽  
Expression Patterns ◽  
Critical Role ◽  
Tumour Suppressor Genes ◽  
Normal Cells ◽  
Control Of Gene Expression ◽  
Cpg Island Methylation

The role of DNA methylation in the control of mammalian gene expression has been the subject of intensive research in recent years, partly due to the critical role of CpG island methylation in the inactivation of tumour suppressor genes during the development of cancer. However, this research has also helped elucidate the role that DNA methylation plays in normal cells. At present, it is also clear that DNA methylation forms an important part of the normal cell-regulatory processes that govern gene transcription. Methylation, targeted at CpG islands, is an important part of the mechanisms that govern X-chromosome inactivation; it is also essential for the maintenance of imprinted genes and, at least in some cases, is critical in determining the cell-type-specific expression patterns of genes. Study of these examples will be important in identifying the mechanisms that control targeting of DNA methylation and how these processes are disrupted during disease pathogenesis.

scholarly journals The Mycobacterium tuberculosis sRNA F6 regulates expression of groEL/S

2020 ◽  
Author(s):  
Joanna Houghton ◽  
Angela Rodgers ◽  
Graham Rose ◽  
Kristine B. Arnvig
Keyword(s):  
Gene Expression ◽  
Mycobacterium Tuberculosis ◽  
Small Rnas ◽  
Transcriptional Control ◽  
Cold Shock ◽  
Control Of Gene Expression ◽  
Rna Biology ◽  
Mouse Model Of Infection

ABSTRACTAlmost 140 years after the identification of Mycobacterium tuberculosis as the etiological agent of tuberculosis, important aspects of its biology remain poorly described. Little is known about the role of post-transcriptional control of gene expression and RNA biology, including the role of most of the small RNAs (sRNAs) identified to date. We have carried out a detailed investigation of the M. tuberculosis sRNA, F6, and show it to be dependent on SigF for expression and significantly induced during in vitro starvation and in a mouse model of infection. However, we found no evidence of attenuation of a ΔF6 strain within the first 20 weeks of infection. A further exploration of F6 using in vitro models of infection suggests a role for F6 as a highly specific regulator of the heat shock repressor, HrcA. Our results point towards a role for F6 during periods of low metabolic activity similar to cold shock and associated with nutrient starvation such as that found in human granulomas in later stages of infection.

scholarly journals Intrusion of a DNA Repair Protein in the RNome World: Is This the Beginning of a New Era?

2009 ◽  
Vol 30 (2) ◽  
pp. 366-371 ◽  
Author(s):  
Gianluca Tell ◽  
David M. Wilson ◽  
Chow H. Lee
Keyword(s):  
Gene Expression ◽  
Dna Repair ◽  
Mrna Level ◽  
Rna Metabolism ◽  
Coding Region ◽  
Control Of Gene Expression ◽  
Dna And Rna ◽  
New Findings

ABSTRACT Apurinic/apyrimidinic endonuclease 1 (APE1), an essential protein in mammals, is known to be involved in base excision DNA repair, acting as the major abasic endonuclease; the protein also functions as a redox coactivator of several transcription factors that regulate gene expression. Recent findings highlight a novel role for APE1 in RNA metabolism. The new findings are as follows: (i) APE1 interacts with rRNA and ribosome processing protein NPM1 within the nucleolus; (ii) APE1 interacts with proteins involved in ribosome assembly (i.e., RLA0, RSSA) and RNA maturation (i.e., PRP19, MEP50) within the cytoplasm; (iii) APE1 cleaves abasic RNA; and (iv) APE1 cleaves a specific coding region of c-myc mRNA in vitro and influences c-myc mRNA level and half-life in cells. Such findings on the role of APE1 in the posttranscriptional control of gene expression could explain its ability to influence diverse biological processes and its relocalization to cytoplasmic compartments in some tissues and tumors. In addition, we propose that APE1 serves as a “cleansing” factor for oxidatively damaged abasic RNA, establishing a novel connection between DNA and RNA surveillance mechanisms. In this review, we introduce questions and speculations concerning the role of APE1 in RNA metabolism and discuss the implications of these findings in a broader evolutionary context.

scholarly journals Autoregulation Is Essential for Precise Temporal and Steady-State Regulation by the Bordetella BvgAS Phosphorelay

2006 ◽  
Vol 189 (5) ◽  
pp. 1974-1982 ◽  
Author(s):  
Corinne L. Williams ◽  
Peggy A. Cotter
Keyword(s):  
Gene Expression ◽  
Steady State ◽  
Response Regulator ◽  
Expression Patterns ◽  
State Regulation ◽  
Temporal Expression ◽  
Multiple Gene ◽  
Insight Into

ABSTRACT The Bordetella BvgAS virulence control system is prototypical of phosphorelays that use a polydomain sensor and a response regulator to control gene expression in response to environmental cues. BvgAS controls the expression of at least three distinct phenotypic phases (Bvg−, Bvgi, and Bvg+) by differentially regulating the expression of at least four classes of genes. Among the loci regulated by BvgAS is bvgAS itself. We investigated the role of autoregulation in the ability of BvgAS to control multiple gene expression patterns in a temporal and steady-state manner by constructing Bordetella bronchiseptica strains in which the bvgAS promoter was replaced with constitutively active promoters. Our results show that positive autoregulation of bvgAS transcription is required for the temporal expression of multiple phenotypic phases that occurs in response to a shift from Bvg−-phase conditions to Bvg+-phase conditions. Autoregulation was also shown to contribute to steady-state regulation; it influences the sensitivity of the system in response to subtle differences in signal intensity. In addition, considered in relation to BvgA and BvgS activities demonstrated in vitro, our results provide insight into how BvgA and BvgS function mechanistically.

scholarly journals Gene expression and DNA methylation altering lead to the high oil content in wild allotetraploid peanut (A. monticola)

2022 ◽  
Author(s):  
Nian Liu ◽  
Manish Pandey ◽  
Bei Wu ◽  
Li Huang ◽  
Huaiyong Luo ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Transcription Factors ◽  
Arachis Hypogaea ◽  
Oil Content ◽  
Expression Patterns ◽  
Gene Clusters ◽  
Oil Accumulation ◽  
Species Specific ◽  
Wild Peanut

Abstract The wild allotetraploid peanut Arachis monticola contains higher oil content than cultivated allotetraploid Arachis hypogaea. To investigate its molecular mechanism controlling oil accumulation, we performed comparative transcriptomics from developing seeds between three Arachis monticola and five Arachis hypogaea varieties. The analysis not only showed species-specific grouping based on transcriptional profiles but also detected two gene clusters with divergent expression patterns enriched in lipid metabolism. Further, the differential expression gene analysis also indicated expression alteration in wild peanut leading to enhanced activity of oil biogenesis and limiting the rate of lipid degradation. We also constructed a regulatory network of lipid metabolic DEGs with co-expressed transcription factors. In addition, bisulfite sequencing was conducted to characterize the variation of DNA methylation between wild allotetraploid (245, WH 10025) and cultivated allotetraploid (Z16, Zhh 7720) genotypes. Genome-wide DNA methylation was found antagonistically correlated with gene expression during seed development. The results indicated that CG and CHG contexts methylation may negatively regulate specific lipid metabolic genes and transcription factors to subtly affect the difference of oil accumulation. Our work provided the first glimpse on the regulatory mechanism of gene expression altering for oil accumulation in wild peanut and gene resources for future breeding applications.

scholarly journals 5-Azacytidine: A Promoter of Epigenetic Changes in the Quest to Improve Plant Somatic Embryogenesis

2018 ◽  
Vol 19 (10) ◽  
pp. 3182 ◽  
Author(s):  
Pedro Osorio-Montalvo ◽  
Luis Sáenz-Carbonell ◽  
Clelia De-la-Peña
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Somatic Embryogenesis ◽  
Regulation Of Gene Expression ◽  
Culture Conditions ◽  
Short Time ◽  
Time Frames ◽  
Different Sources

Somatic embryogenesis (SE) is a widely studied process due to its biotechnological potential to generate large quantities of plants in short time frames and from different sources of explants. The success of SE depends on many factors, such as the nature of the explant, the microenvironment generated by in vitro culture conditions, and the regulation of gene expression, among others. Epigenetics has recently been identified as an important factor influencing SE outcome. DNA methylation is one of the most studied epigenetic mechanisms due to its essential role in gene expression, and its participation in SE is crucial. DNA methylation levels can be modified through the use of drugs such as 5-Azacytidine (5-AzaC), an inhibitor of DNA methylation, which has been used during SE protocols. The balance between hypomethylation and hypermethylation seems to be the key to SE success. Here, we discuss the most prominent recent research on the role of 5-AzaC in the regulation of DNA methylation, highlighting its importance during the SE process. Also, the molecular implications that this inhibitor might have for the increase or decrease in the embryogenic potential of various explants are reviewed.

scholarly journals Complex Relationships between Chromatin Accessibility, Sequence Divergence, and Gene Expression in Arabidopsis thaliana

2017 ◽  
Vol 35 (4) ◽  
pp. 837-854 ◽  
Author(s):  
Cristina M Alexandre ◽  
James R Urton ◽  
Ken Jean-Baptiste ◽  
John Huddleston ◽  
Michael W Dorrity ◽  
...  
Keyword(s):  
Gene Expression ◽  
Arabidopsis Thaliana ◽  
Transcription Factors ◽  
Dna Sequences ◽  
Sequence Variation ◽  
Expression Patterns ◽  
Sequence Divergence ◽  
Chromatin Accessibility ◽  
Regulatory Dna ◽  
Regulatory Sites

AbstractVariation in regulatory DNA is thought to drive phenotypic variation, evolution, and disease. Prior studies of regulatory DNA and transcription factors across animal species highlighted a fundamental conundrum: Transcription factor binding domains and cognate binding sites are conserved, while regulatory DNA sequences are not. It remains unclear how conserved transcription factors and dynamic regulatory sites produce conserved expression patterns across species. Here, we explore regulatory DNA variation and its functional consequences within Arabidopsis thaliana, using chromatin accessibility to delineate regulatory DNA genome-wide. Unlike in previous cross-species comparisons, the positional homology of regulatory DNA is maintained among A. thaliana ecotypes and less nucleotide divergence has occurred. Of the ∼50,000 regulatory sites in A. thaliana, we found that 15% varied in accessibility among ecotypes. Some of these accessibility differences were associated with extensive, previously unannotated sequence variation, encompassing many deletions and ancient hypervariable alleles. Unexpectedly, for the majority of such regulatory sites, nearby gene expression was unaffected. Nevertheless, regulatory sites with high levels of sequence variation and differential chromatin accessibility were the most likely to be associated with differential gene expression. Finally, and most surprising, we found that the vast majority of differentially accessible sites show no underlying sequence variation. We argue that these surprising results highlight the necessity to consider higher-order regulatory context in evaluating regulatory variation and predicting its phenotypic consequences.

scholarly journals Genomic DNA microarray comparison of gene expression patterns in Paracoccidioides brasiliensis mycelia and yeasts in vitro

Microbiology ◽  
2009 ◽  
Vol 155 (8) ◽  
pp. 2795-2808 ◽  
Author(s):  
Jomar Patrício Monteiro ◽  
Karl V. Clemons ◽  
Laurence F. Mirels ◽  
John A. Coller ◽  
Thomas D. Wu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factors ◽  
Genomic Dna ◽  
Paracoccidioides Brasiliensis ◽  
Expression Patterns ◽  
Gene Expression Patterns ◽  
Protein Catabolism ◽  
Time Points ◽  
Over Time

Paracoccidioides brasiliensis is a thermally dimorphic fungus, and causes the most prevalent systemic mycosis in Latin America. Infection is initiated by inhalation of conidia or mycelial fragments by the host, followed by further differentiation into the yeast form. Information regarding gene expression by either form has rarely been addressed with respect to multiple time points of growth in culture. Here, we report on the construction of a genomic DNA microarray, covering approximately 25 % of the genome of the organism, and its utilization in identifying genes and gene expression patterns during growth in vitro. Cloned, amplified inserts from randomly sheared genomic DNA (gDNA) and known control genes were printed onto glass slides to generate a microarray of over 12 000 elements. To examine gene expression, mRNA was extracted and amplified from mycelial or yeast cultures grown in semi-defined medium for 5, 8 and 14 days. Principal components analysis and hierarchical clustering indicated that yeast gene expression profiles differed greatly from those of mycelia, especially at earlier time points, and that mycelial gene expression changed less than gene expression in yeasts over time. Genes upregulated in yeasts were found to encode proteins shown to be involved in methionine/cysteine metabolism, respiratory and metabolic processes (of sugars, amino acids, proteins and lipids), transporters (small peptides, sugars, ions and toxins), regulatory proteins and transcription factors. Mycelial genes involved in processes such as cell division, protein catabolism, nucleotide biosynthesis and toxin and sugar transport showed differential expression. Sequenced clones were compared with Histoplasma capsulatum and Coccidioides posadasii genome sequences to assess potentially common pathways across species, such as sulfur and lipid metabolism, amino acid transporters, transcription factors and genes possibly related to virulence. We also analysed gene expression with time in culture and found that while transposable elements and components of respiratory pathways tended to increase in expression with time, genes encoding ribosomal structural proteins and protein catabolism tended to sharply decrease in expression over time, particularly in yeast. These findings expand our knowledge of the different morphological forms of P. brasiliensis during growth in culture.

199 IN VITRO-DEVELOPED BOVINE BLASTOCYSTS ARE MARKED WITH ABERRANT HYPER- AND HYPO-METHYLATED GENOMIC REGIONS

2015 ◽  
Vol 27 (1) ◽  
pp. 190
Author(s):  
D. Salilew-Wondim ◽  
M. Hoelker ◽  
U. Besenfelder ◽  
V. Havlicek ◽  
F. Rings ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Expression Patterns ◽  
Proximal Promoter ◽  
Altered Gene Expression ◽  
Genome Wide ◽  
Altered Gene ◽  
Genomic Regions

Most often, in vitro produced embryos display poor quality and altered gene expression patterns compared to their in vivo counterparts. Aberrant DNA methylation occurring during in vitro embryo development is believed to be one of the multifaceted factors which may cause altered gene expression and poor embryo quality. Here, we investigated the genome-wide DNA methylation patterns of in vitro derived embryos using the recently developed Bovine EmbryoGENE Methylation Platform (BEGMP) array (Shojaei Saadi et al. BMC Genomics 2014 15, 451. doi: 10.1186/1471-2164-15-451) to unravel the aberrantly methylated genomic region in in vitro developed embryos. For this, in vitro and in vivo produced blastocysts were produced and used for genome-wide DNA methylation analysis. In vitro blastocysts were produced from oocytes retrieved from ovaries collected from the local abattoir and matured, fertilized, and cultured in vitro using SOF media. The in vivo blastocysts were produced by superovulation and AI of Simmental heifers followed by uterine flushing. Genomic DNA (gDNA) was then isolated from four replicates (each 10 blastocysts) of in vivo and in vitro derived blastocysts using Allprep DNA/RNA micro kit (Qiagen, Valencia, CA, USA) and the gDNA was then fragmented using the MseI enzyme. Following this, MseLig21 and MseLig were ligated to the MseI-digested genomic fragments in the presence of Ligase enzyme. Methyl-sensitive enzymes, HpaII, AciI, and Hinp1I, were used to cleave unmethlayted genomic regions within the MseI-MseI region of the fragmented DNA. The gDNA was subjected to two rounds of ligation-mediated polymerase chain reaction (LM-PCR) amplification. After removal of the adapters, the amplified gDNA samples from in vivo or in vitro groups were labelled either Cy-3 or Cy-5 dyes in dye-swap design using ULS Fluorescent gDNA labelling kit (Kreatech Biotechnology BV, Amsterdam, The Netherlands). Hybridization was performed for 40 h at 65°C. Slides were scanned using Agilent's High-Resolution C Scanner (Agilent Technologies Inc., Santa Clara, CA, USA) and features were extracted with Agilent's Feature Extraction software (Agilent Technologies Inc.). The results have shown that from a total of 414 566 probes harboured by the BEGMP array, 248 453 and 253 147 probes were detected in in vitro and in vivo derived blastocysts, respectively. Data analysis using the linear modelling for microarray (LIMMA) package and R software (The R Project for Statistical Computing, Vienna, Austria) revealed a total of 3434 differentially methylated regions (DMRs; Fold change ≥1.5, P-value <0.05), of which 42 and 58% were hyper- and hypo-methylated, respectively, in in vitro derived blastocysts compared to their in vivo counterparts. The DMRs were found to be localised in the intronic, exonic, promoter, proximal promoter, and distal promoter, and some of the probes did not have nearby genes. In addition, 10.8% of the DMRs were found to be stretched in short, long, or intermediate CpG islands. Thus, this study demonstrated genome-wide dysregulation in the epigenome landscape of in vitro-derived embryos by the time they reach to the blastocysts stage.

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