After the last email (about “instinct” clearly involving epigenetic effects) –– the attached pdf file contains one editorial followed by three papers on different phenotypes being elicited by epigenetics effects. Every cell in an organism (except mammalian red cells) contains the same DNA, but only a subset of genes is expressed in each cell type. And there are 200-215 differnt cell types; this means humans have one haploid genome, but 200-215 distinctly different epigenomes.
DNA is packaged into chromatin, the core component of which is the nucleosome. During development and cell differentiation, histone constituents (proteins) of nucleosomes are modified by methylation, acetylation, or phosphorylation of specific amino acids. Different modifications are associated with activating or silencing genes. Repressive chromatin marks are thought to constitute the epigenetic memory of the silenced transcriptional state. How are silent chromatin domains maintained –– during DNA replication and cell division to the next generation? The three papers following the editorial reveal that long-term stable transmission of “the silenced state” requires sequence-specific recruitment of histone-modifying enzymes.
Histone modifications that repress gene expression include methylation of histone H3 on lysine 9 or 27 (H3K9me2/3 or H3K27me3). The enzymes that methylate H3 are recruited to DNA by proteins or RNA, and act on flanking nucleosomes to create a repressed domain. These regions are called heterochromatin, or Polycomb protein (PcP) domains. In yeast (first paper), the mating-type locus (mat) is silenced by formation of a heterochromatin domain. In the fruit fly (second paper), developmental loci are silenced by the PcPs. In both systems, cis-acting DNA elements and DNA-binding proteins set up the silent domains. Difference in the decay rate of H3K27me3 in the two studies is likely due to sequences within the Ubx enhancers that either recruit or stabilize PRC2 binding. Similarly, authors of the third paper found that in yeast, in addition to DNA-binding sites for the known methyltransferase recruiter –– additional, unidentified sequences within the mat locus somehow promote propagation of the repressive mark(s) in chromatin.
Science 7 Apr 2o17; 356: p. 41 & 85–88 & 88–91 [three articles] & 28-29 [ed.]