What is Epigenetics?

Mutational refers to mechanisms that regulate gene expression without altering the underlying DNA sequence. Epigenetic changes determine which genes are "turned on" or "off" and when, and can be influenced by both environmental and genetic factors. The literal meaning of "mutational" is "above" or "in addition to genetics", referring to heritable changes in gene function that do not involve alterations to the genetic code itself.

DNA Methylation

One of the primary Epigenetics mechanisms is DNA methylation. DNA methylation involves the addition of a methyl group to cytosine bases in the DNA molecule. When methyl groups are added to promoter regions of genes, they typically act to suppress gene transcription. High levels of methylation in a gene's promoter thus leads to silencing or decreased expression of that gene. DNA methylation plays a key role in processes like genomic imprinting, X-chromosome inactivation, and suppression of repetitive elements. It is also involved in regulating tissue-specific gene expression patterns during development. Environmental factors during development can influence DNA methylation patterns which may persist throughout life.

Histone Modifications

Another major category of epigenetic marks is covalent histone modifications. Histones are proteins around which DNA winds to form chromatin and nucleosomes. Histone modifications such as acetylation, phosphorylation and methylation determine how tightly or loosely DNA is wound around histones. These modifications can affect gene expression by altering chromatin structure in a way that makes genes more or less accessible to transcription machinery. For example, histone acetylation generally marks actively transcribed regions, while methylation can either activate or repress gene expression depending on which amino acid residues are modified. Histone modifications are established and interpreted by complexes of enzymes working in a coordinated manner.

Non-coding RNAs

Non-coding RNA molecules like microRNAs and long non-coding RNAs also play important epigenetic roles by guiding other proteins to complementary DNA or mRNA sequences and regulating gene expression at the post-transcriptional level. MicroRNAs target mRNAs for degradation or translational repression via base pairing with sequences typically located in the 3' untranslated region (UTR) of mRNAs. This provides an additional layer of epigenetic control over mRNA levels and protein output. Many long non-coding RNAs help to recruit or guide histone modifying complexes to specific genomic loci, leading to activation or repression of nearby genes. Non-coding RNAs mediate important cell fate decisions and maintain cellular identity.

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