Concepts Summary

• The term epigenetics, first coined by Conrad Waddington, today refers to effects by which phenotypes are passed to other cells or future generations but do not include differences in the base sequence of DNA.
• Many epigenetic phenotypes result from changes to chromatin structure. Epigenetic effects occur through DNA methylation, histone modification, and RNA molecules.
• Epigenetic changes are stable but are potentially affected by environmental factors.
• Three molecular mechanisms underlie many epigenetic phenotypes: (1) changes in patterns of DNA methylation; (2) chemical modifications of histone proteins; and (3) RNA molecules that affect chromatin structure and gene expression.
• Some epigenetic effects result from DNA methylation, in which cytosine bases are methylated to form 5-methylcytosine. Methylation often occurs at CpG dinucleotides. The presence of 5-methylcytosine is associated with repression of transcription.
• DNA regions with many CpG dinucleotides are referred to as CpG islands. Methylation of CpG islands near a gene often leads to repression of transcription.
• DNA methylation inhibits transcription by inhibiting the binding of transcription factors and others proteins required for transcription to occur. DNA methylation also attracts proteins that repress transcription and histone deacetylase enzymes that alter chromatin structure.
• DNA methylation is maintained across cell division by methyltransferase enzymes that recognize methylation of CpG dinucleotides on one strand of DNA and add methyl groups to the unmethylated cytosine bases on the other strand.
• Modifications of histone proteins alter chromatin structure. Histone modifications may be passed across cell division.
• RNA molecules bring about modification of chromatin by a variety of processes.
• Paramutation is a heritable alteration of one allele by another allele, without any change in DNA sequence. Paramutation in corn and mice is mediated through small RNA molecules.
• Early life experiences can produce epigenetic changes that have long-lasting effects on behavior.
• Environmental chemicals may produce epigenetic effects that are passed to later generations.
• Epigenetic modifications have effects on metabolism that extend across generations.
• Phenotypic differences between genetically identical monozygotic twins may result from epigenetic effects.
• X inactivation occurs when one X chromosome in female cells is permanently silenced. Epigenetic changes bring about X inactivation and require the action of several genes that encode long noncoding RNAs.
• Genomic imprinting occurs when the expression of a gene depends on which parent transmitted the gene. It is caused by epigenetic changes to chromatin structure that are passed to offspring. The genetic conflict hypothesis suggests that imprinting evolves because of conflicting evolutionary pressures acting on maternal and paternal alleles.
• The epigenome is the complete set of chromatin modifications possessed by an individual organism.