Epigenetics

Epigenetics refers to heritable changes in gene expression that do not involve changes to the underlying DNA sequence. These changes influence how genes are turned on or off and how cells with the same genome can have different functions. Epigenetic information is stored in chemical marks on DNA and histone proteins, as well as in RNA molecules, collectively shaping the epigenome.

Primary mechanisms include DNA methylation, typically the addition of methyl groups to cytosine bases in CpG dinucleotides, which often represses transcription; histone modifications such as acetylation and methylation, which alter chromatin structure and accessibility; ATP-dependent chromatin remodeling; and non-coding RNAs that regulate gene expression at transcriptional and post-transcriptional levels.

Maintenance and inheritance: Many epigenetic marks are established during development and are propagated during cell division. Some marks can be transmitted across generations, though the extent and mechanisms of transgenerational inheritance are debated.

Influences and roles: Epigenetic regulation is essential for development, imprinting, and X-chromosome inactivation. Environmental factors including diet, toxins, stress, and aging can modify epigenetic marks, linking environment to gene expression. Abnormal epigenetic regulation is associated with diseases such as cancer, neurodevelopmental disorders, and metabolic conditions.

Research and applications: Epigenetic studies use tools like bisulfite sequencing, chromatin immunoprecipitation followed by sequencing (ChIP-seq), and assays for transposase-accessible chromatin (ATAC-seq). Epigenetic therapies include inhibitors of DNA methyltransferases and histone deacetylases, approved for certain cancers.

History and scope: The term derives from Waddington's metaphor of the epigenotype; the field has expanded to map the human epigenome and understand development, aging, and disease.