DNA Methylation and Its Basic Function

DNA Methylation and Its Basic Function

2013 | Lisa D Moore, Thuc Le and Guoping Fan
DNA methylation is an epigenetic process that involves the addition of a methyl group to cytosine residues, forming 5-methylcytosine (5mC). This process regulates gene expression by recruiting proteins involved in gene repression or by inhibiting the binding of transcription factors to DNA. During development, DNA methylation patterns change dynamically, leading to stable, tissue-specific methylation patterns in differentiated cells. In the nervous system, DNA methylation and demethylation are crucial for neural development and function. DNA methyltransferases (Dnmts) are responsible for adding methyl groups, while demethylation involves enzymes that modify 5mC to facilitate its removal. Postmitotic neurons continue to express Dnmts, suggesting a role in brain function. Neuronal activity can modulate DNA methylation in response to environmental stimuli, and precise regulation of DNA methylation is essential for normal cognitive function. Alterations in DNA methylation due to developmental mutations or environmental factors can lead to mental impairments. DNA methylation is involved in silencing retroviral elements, regulating gene expression, genomic imprinting, and X chromosome inactivation. It plays a role in intergenic regions by repressing harmful genetic elements and in CpG islands by regulating gene expression and imprinting. Gene body methylation is associated with gene expression in dividing cells but not in non-dividing cells like the brain. DNA methylation is regulated by writers, erasers, and readers, with Dnmts being key writers. Dnmt1 maintains methylation during DNA replication, while Dnmt3a and Dnmt3b establish new methylation patterns. DNA demethylation can occur passively or actively, with active demethylation involving enzymes like AID/APOBEC and Tet enzymes. The BER pathway is involved in demethylation by cleaving modified bases. Methyl-binding proteins like MBDs and UHRF proteins recognize methylated DNA and influence gene expression. DNA methylation interacts with histone modifications and miRNAs to regulate gene expression. In the brain, DNA methylation is crucial for neuronal differentiation and maturation. Conditional knockout studies show the importance of Dnmts in neural development. MeCP2, a methyl-binding protein, is essential for neuronal maturation and its dysfunction leads to Rett Syndrome. DNA methylation in the adult brain is studied using pharmacological inhibitors and conditional knockout models. Neuronal activity influences DNA methylation, affecting gene expression and synaptic plasticity. DNA methylation plays a role in learning and memory, and its dysregulation is associated with neurological and psychiatric disorders.DNA methylation is an epigenetic process that involves the addition of a methyl group to cytosine residues, forming 5-methylcytosine (5mC). This process regulates gene expression by recruiting proteins involved in gene repression or by inhibiting the binding of transcription factors to DNA. During development, DNA methylation patterns change dynamically, leading to stable, tissue-specific methylation patterns in differentiated cells. In the nervous system, DNA methylation and demethylation are crucial for neural development and function. DNA methyltransferases (Dnmts) are responsible for adding methyl groups, while demethylation involves enzymes that modify 5mC to facilitate its removal. Postmitotic neurons continue to express Dnmts, suggesting a role in brain function. Neuronal activity can modulate DNA methylation in response to environmental stimuli, and precise regulation of DNA methylation is essential for normal cognitive function. Alterations in DNA methylation due to developmental mutations or environmental factors can lead to mental impairments. DNA methylation is involved in silencing retroviral elements, regulating gene expression, genomic imprinting, and X chromosome inactivation. It plays a role in intergenic regions by repressing harmful genetic elements and in CpG islands by regulating gene expression and imprinting. Gene body methylation is associated with gene expression in dividing cells but not in non-dividing cells like the brain. DNA methylation is regulated by writers, erasers, and readers, with Dnmts being key writers. Dnmt1 maintains methylation during DNA replication, while Dnmt3a and Dnmt3b establish new methylation patterns. DNA demethylation can occur passively or actively, with active demethylation involving enzymes like AID/APOBEC and Tet enzymes. The BER pathway is involved in demethylation by cleaving modified bases. Methyl-binding proteins like MBDs and UHRF proteins recognize methylated DNA and influence gene expression. DNA methylation interacts with histone modifications and miRNAs to regulate gene expression. In the brain, DNA methylation is crucial for neuronal differentiation and maturation. Conditional knockout studies show the importance of Dnmts in neural development. MeCP2, a methyl-binding protein, is essential for neuronal maturation and its dysfunction leads to Rett Syndrome. DNA methylation in the adult brain is studied using pharmacological inhibitors and conditional knockout models. Neuronal activity influences DNA methylation, affecting gene expression and synaptic plasticity. DNA methylation plays a role in learning and memory, and its dysregulation is associated with neurological and psychiatric disorders.
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