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The molecular basis of the organization of repetitive DNA-containing constitutive heterochromatin in mammals

Author:
Nishibuchi, Gohei, Déjardin, Jérôme
Source:
Chromosome research 2017 v.25 no.1 pp. 77-87
ISSN:
0967-3849
Subject:
databases, epigenetics, essential genes, eukaryotic cells, heterochromatin, histones, humans, intergenic DNA, methylation, molecular models, precipitin tests, satellite DNA, telomeres, transposons, yeasts
Abstract:
Constitutive heterochromatin is composed mainly of repetitive elements and represents the typical inert chromatin structure in eukaryotic cells. Approximately half of the mammalian genome is made of repeat sequences, such as satellite DNA, telomeric DNA, and transposable elements. As essential genes are not present in these regions, most of these repeat sequences were considered as junk DNA in the past. However, it is now clear that these regions are essential for chromosome stability and the silencing of neighboring genes. Genetic and biochemical studies have revealed that histone methylation at H3K9 and its recognition by heterochromatin protein 1 represent the fundamental mechanism by which heterochromatin forms. Although this molecular mechanism is highly conserved from yeast to human cells, its detailed epigenetic regulation is more complex and dynamic for each distinct constitutive heterochromatin structure in higher eukaryotes. It can also vary according to the developmental stage. Chromatin immunoprecipitation followed by sequencing (ChIP-seq) analysis is a powerful tool to investigate the epigenetic regulation of eukaryote genomes, but non-unique reads are usually discarded during standard ChIP-seq data alignment to reference genome databases. Therefore, specific methods to obtain global epigenetic information concerning repetitive elements are needed. In this review, we focus on such approaches and we summarize the latest molecular models for distinct constitutive heterochromatin types in mammals.
Agid:
5757076