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

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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.

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Abbreviations

ADD:

ATRX-DNMT3-DNMTT3L

ALT:

Alternative lengthening of telomeres

ATRX:

α-Thalassemia/mental retardation X-linked

BEND3:

BEN domain containing 3

DAXX:

Death domain-associated protein

ERV:

Endogenous retrovirus

HUSH:

Human-silencing hub

HP1:

Heterochromatin protein 1

IAP:

Intracisternal A particle

KAP1:

KRAB-ZFP-associated protein 1

KRAB-ZFP:

Krüppel-associated box domain-zinc finger proteins

LINE:

Long-interspersed nucleotide element

LTR:

Long terminal repeat

Mommes:

Modifiers of murine metastable epialleles

NuRD:

Nucleosome remodeling and deacetylase complex

ORC:

Origin recognition complex

Pc:

Polycomb

PEV:

Position effect variegation

PICh:

Proteomics of isolated chromatin segment

piRNA:

PIWI-interacting RNA

PIWI:

P-element-induced wimpy testis

POT1:

Protection of telomeres 1

RAP1:

Repressor and activator protein 1

SAHF:

Senescence-associated heterochromatic foci

SETDB1:

SET domain bifurcated 1

Su(var):

Suppressor of variegation

TERRA:

Telomere repeat-containing RNA

TIN2:

TRF1­interacting nuclear protein 2

TPP1:

POT1- and TIN2-interacting protein

TRF1:

Telomeric repeat-binding factor 1

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  1. Biology of Repetitive Sequences, CNRS UPR1142, 141 rue de la Cardonille, 34000, Montpellier, France

    Gohei Nishibuchi & Jérôme Déjardin

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  1. Gohei Nishibuchi
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  2. Jérôme Déjardin
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Correspondence to Jérôme Déjardin.

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Nishibuchi, G., Déjardin, J. The molecular basis of the organization of repetitive DNA-containing constitutive heterochromatin in mammals. Chromosome Res 25, 77–87 (2017). https://doi.org/10.1007/s10577-016-9547-3

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