scholarly journals DNA metylation as one of the main mechanisms of gene activity regulation

2004 ◽  
Vol 2 (1) ◽  
pp. 27-37
Author(s):  
Anna A Pendina ◽  
Vera V Grinkevich ◽  
Tatyana V Kuznetsova ◽  
Vladislav S Baranov

 DNA methylation is one of the main mechanisms of epigenetic inheritance in eukaryotes. In this review we looked through the ways of 5-methylcytosin origin, it's distribution in genome, the mechanism of gene repression via hypermetilation, the role of metylation in genomic imprinting and in X-chromosome inactivation, in embryogenesis of mammals, in the processes of oncogenesis and in etiology of some common human inherited diseases

DNA methylation in mammals is reviewed, and it is concluded that one role of methylation is to aid cell memory, which is defined as the ability of mitotically derived progeny cells to remember and re-establish their proper cellular identity. Methylation of X-linked CpG-rich islands probably stabilizes X-chromosome inactivation, but other mechanisms appear to be involved. Late replication is discussed as a key ancestral mechanism for X inactivation, and it is emphasized that early and late replication domains may each be self perpetuating. Therefore, early-late replication timing becomes another strong candidate mechanism for cell memory. A chromosome-loop folding enigma is discussed, and it is concluded that special mechanisms are needed to explain the formation and maintenance of specific looped domains. DNA reeling, such as done by type I restriction-modification enzymes, is proposed to provide this special mechanism for folding. DNA reeling mechanisms can help to explain the cis -spreading of X-chromosome inactivation as well as long-range action by enhancers.


2006 ◽  
Vol 2006 ◽  
pp. 1-6 ◽  
Author(s):  
Mary F. Lyon

There is longstanding evidence that X-chromosome inactivation (XCI) travels less successfully in autosomal than in X-chromosomal chromatin. The interspersed repeat elements LINE1s (L1s) have been suggested as candidates for “boosters” which promote the spread of XCI in the X-chromosome. The present paper reviews the current evidence concerning the possible role of L1s in XCI. Recent evidence, accruing from the human genome sequencing project and other sources, confirms that mammalian X-chromosomes are indeed rich in L1s, except in regions where there are many genes escaping XCI. The density of L1s is the highest in the evolutionarily oldest regions. Recent work on X; autosome translocations in human and mouse suggested failure of stabilization of XCI in autosomal material, so that genes are reactivated, but resistance of autosomal genes to the original silencing is not excluded. The accumulation of L1s on the X-chromosome may have resulted from reduced recombination or late replication. Whether L1s are part of the mechanism of XCI or a result of it remains enigmatic.


Changing DNA methylation patterns during embryonic development are discussed in relation to differential gene expression, changes in X-chromosome activity and genomic imprinting. Sperm DNA is more methylated than oocyte DNA, both overall and for specific sequences. The methylation difference between the gametes could be one of the mechanisms (along with chromatin structure) regulating initial differences in expression of parental alleles in early development. There is a loss of methylation during development from the morula to the blastocyst and a marked decrease in methylase activity. De novo methylation becomes apparent around the time of implantation and occurs to a lesser extent in extra-embryonic tissue DNA. In embryonic DNA, de novo methylation begins at the time of random X-chromosome inactivation but it continues to occur after X-chromosome inactivation and may be a mechanism that irreversibly fixes specific patterns of gene expression and X-chromosome inactivity in the female. The germ line is probably delineated before extensive de novo methylation and hence escapes this process. The marked undermethylation of the germ line DNA may be a prerequisite for X-chromosome reactivation. The process underlying reactivation and removal of parent-specific patterns of gene expression may be changes in chromatin configuration associated with meiosis and a general reprogramming of the germ line to developmental totipotency.


Aging ◽  
2015 ◽  
Vol 7 (8) ◽  
pp. 568-578 ◽  
Author(s):  
Davide Gentilini ◽  
Paolo Garagnani ◽  
Serena Pisoni ◽  
Maria Giulia Bacalini ◽  
Luciano Calzari ◽  
...  

2020 ◽  
Author(s):  
Surbhi Kohli ◽  
Parul Gulati ◽  
Jayant Maini ◽  
Shamsudheen KV ◽  
Rajesh Pandey ◽  
...  

AbstractIn mealybugs, transcriptional inactivation of the entire paternal genome in males, due to genomic imprinting, is closely correlated with sex determination. The sequencing, de-novo assembly and annotation of the mealybug, Maconellicoccus hirsutus genome and its comparison with Planococcus citri genome strengthened our gene identification. The expanded gene classes, in both genomes relate to the high pesticide and radiation resistance; the phenotypes correlating with increased gene copy number rather than the acquisition of novel genes. The complete repertoire of genes for epigenetic regulation and multiple copies of genes for the core members of polycomb and trithorax complexes and the canonical chromatin remodelling complexes are present in both the genomes. Phylogenetic analysis with Drosophila shows high conservation of most genes, while a few have diverged outside the functional domain. The proteins involved in mammalian X-chromosome inactivation are identified in mealybugs, thus demonstrating the evolutionary conservation of factors for facultative heterochromatization. The transcriptome analysis of adult male and female M.hirsutus indicates the expression of the epigenetic regulators and the differential expression of metabolic pathway genes and the genes for sexual dimorphism. The depletion of endosymbionts in males during development is reflected in the significantly lower expression of endosymbiont genes in them.Author summaryThe mealybug system offers a unique model for genomic imprinting and differential regulation of homologous chromosomes that pre-dates the discovery of dosage compensation of X chromosomes in female mammals. In the absence of robust genetics for mealybugs, we generated and analysed the genome and transcriptome profile as primary resources for effective exploration. The expanded gene classes in the mealybugs relate to their unique biology; the expansion of pesticide genes, trehalose transporter, SETMAR and retrotransposons correlate with pesticide, desiccation and radiation resistance, respectively. The similarity in the genomic profile of two species of mealybugs strengthens our gene prediction. All the known epigenetic modifiers and proteins of the primary complexes like the PRC1,2 and the trithorax are conserved in mealybugs, so also the homologues of mammalian proteins involved in X chromosome inactivation. The high copy number of genes for many partners in these complexes could facilitate the inactivation of a large part of the genome and raise the possibility of formation of additional non-canonical complexes for sex specific chromosome inactivation. In adult males and females, the status of epigenetic regulation is likely to be in a maintenance state; therefore, it is of interest to analyze the expression of epigenetic regulators during development.


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