ReviewEpigenetic Regulation in Human Brain—Focus on Histone Lysine Methylation
Section snippets
Histone Modifications
The nucleosome as the elementary unit of chromatin comprises 146 base pair (bp) of DNA wrapped around an octamer of four different histone proteins (H2A, H2B, H3, and H4) (17). Both the nucleosome core histones and some of their variants (H3.1, H3.3, etc) are subject to covalent modifications of specific residues located primarily at the amino-terminal tail; these include lysine acetylation, methylation, SUMOylation, and ubiquitinylation; arginine methylation; serine phosphorylation; and
Methodological Considerations and Limitations
Histones are bound with very high affinity to genomic DNA (51), and so it is not surprising that bulk levels of nucleosome-bound DNA remain relatively unchanged, even in brain tissues subject to 30 hours of autolysis (38). However, in a living cell, the chromatin architecture of the interphase nucleus is complex. In addition to an array of subnuclear bodies (e.g., nucleosomes, PML bodies, Cajal bodies), highly organized three-dimensional chromatin domains and transcription factories exist that
Gene Expression in Development and Disease Is Associated with Histone Methylation Changes at Gene Promoters Human Brain
Both the metabotropic (GRM1-7) and ionotropic (e.g., N-methyl d-aspartate, amino-3-hydroxy-5-methylisoxazole propionate, and kainate) glutamate receptor genes undergo dynamic, region- and cell-specific changes in expression during the course of brain development. In human brain, these developmental and region-specific changes of mRNA levels are accompanied by complementary alterations in H3K4 di- and tri-methylation at the sites of the corresponding promoters (31). Likewise, the progressive
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