Chromosome organization and chromatin modification: influence on genome function and evolution

Abstract

Histone modifications of nucleosomes distinguish euchromatic from heterochromatic chromatin states, distinguish gene regulation in eukaryotes from that of prokaryotes, and appear to allow eukaryotes to focus recombination events on regions of highest gene concentrations. Four additional epigenetic mechanisms that regulate commitment of cell lineages to their differentiated states are involved in the inheritance of differentiated states, e.g., DNA methylation, RNA interference, gene repositioning between interphase compartments, and gene replication time. The number of additional mechanisms used increases with the taxon’s somatic complexity. The ability of siRNA transcribed from one locus to target, in trans, RNAi-associated nucleation of heterochromatin in distal, but complementary, loci seems central to orchestration of chromatin states along chromosomes. Most genes are inactive when heterochromatic. However, genes within β-heterochromatin actually require the heterochromatic state for their activity, a property that uniquely positions such genes as sources of siRNA to target heterochromatinization of both the source locus and distal loci. Vertebrate chromosomes are organized into permanent structures that, during S-phase, regulate simultaneous firing of replicon clusters. The late replicating clusters, seen as G-bands during metaphase and as meiotic chromomeres during meiosis, epitomize an ontological utilization of all five self-reinforcing epigenetic mechanisms to regulate the reversible chromatin state called facultative (conditional) heterochromatin. Alternating euchromatin/heterochromatin domains separated by band boundaries, and interphase repositioning of G-band genes during ontological commitment can impose constraints on both meiotic interactions and mammalian karyotype evolution.

Next Generation Sequencing of Serum Circulating Nucleic Acids from Patients with Invasive Ductal Breast Cancer Reveals Differences to Healthy and Nonmalignant Controls

“…Interestingly, extensive hypomethylation of LINE elements and endogenous retroviruses have been found in several cancers (36), and hypomethylation does have an effect on nucleosome positioning (33). Furthermore, LINE elements in humans are predominantly found in chromosomal G bands also known as facultative heterochromatin (37,38). Interestingly, there is evidence of nonrandom degradation of DNA in leukemic cells in which apoptotic DNA preferentially hybridizes to heterochromatin (39).…”

No effect of recombination on the efficacy of natural selection in primates

“…For example, it may be productive to stratify genes based on gene expression (breadth or intensity), as a proxy for selective pressures experienced by a gene, e.g., genes that are broadly expressed are thought to be under more constraint (Duret and Mouchiroud 2000). While such an analysis would clearly be worthwhile, patterns of gene expression are correlated with both gene density and recombination rates (perhaps for mechanistic reasons) (Holmquist and Ashley 2006) and so picking apart the causal factors will likely be challenging.…”

A human B cell methylome at 100−base pair resolution

“…Giemsa staining has been used for many decades to visualize mitotic chromosomes and to detect different chromosomal aberrations, such as translocations and inversions. Darkly stained, late-replicating G-bands and lightly stained, earlyreplicating R-bands reflect different chromatin compaction, replication timing, gene density, and GC content (40). Efforts to trace back Giemsa staining to nucleotide sequence differences have been only moderately successful, and GC-content-based in silico band prediction algorithms produced just weak similarities (41).…”