Heterochromatin: Guardian of the Genome

Abstract

Constitutive heterochromatin is a major component of the eukaryotic nucleus and is essential for the maintenance of genome stability. Highly concentrated at pericentromeric and telomeric domains, heterochromatin is riddled with repetitive sequences and has evolved specific ways to compartmentalize, silence, and repair repeats. The delicate balance between heterochromatin epigenetic maintenance and cellular processes such as mitosis and DNA repair and replication reveals a highly dynamic and plastic chromatin domain that can be perturbed by multiple mechanisms, with far-reaching consequences for genome integrity. Indeed, heterochromatin dysfunction provokes genetic turmoil by inducing aberrant repeat repair, chromosome segregation errors, transposon activation, and replication stress and is strongly implicated in aging and tumorigenesis. Here, we summarize the general principles of heterochromatin structure and function, discuss the importance of its maintenance for genome integrity, and propose that more comprehensive analyses of heterochromatin roles in tumorigenesis will be integral to future innovations in cancer treatment.

Meta‐analysis of the association between chromosomal polymorphisms and outcomes of embryo transfer following in vitro fertilization and/or intracytoplasmic sperm injection

“…Fourth, constitutive heterochromatin predominantly assembles on the telomeric, centromeric, and pericentric regions of chromosomes, where it remains condensed throughout the cell cycle and is important for genome stability and chromosome segregation . Most constitutive heterochromatin is located on chromosomes 1, 9, and 16; the acrocentric chromosomes; and the Y chromosome .…”

Essential roles of Windei and nuclear monoubiquitination of Eggless/ SETDB 1 in transposon silencing

“…Trimethylation of histone 3 lysine 9 (H3K9me3) is a major repressive histone mark, leading to heterochromatin formation and gene silencing [1][2][3]. In Drosophila, H3K9 methylation is governed by three histone methyltransferases (HMTs), Su(var)3-9, G9a, and Eggless/SETDB1 (Egg) [4][5][6][7][8][9][10].…”

The mouse HP1 proteins are essential for preventing liver tumorigenesis

“…Conversely heterochromatin is highly 49 compacted, enriched in repetitive DNA sequences, and mostly silent. Although, 50 heterochromatin was considered for a long time as an inert compartment with the single 51 function of silencing parasite DNA sequences, it is now recognized as a dynamic and 52 functional compartment (Janssen et al, 2018a). Heterochromatin Protein 1 (HP1) proteins 53 were first isolated as major heterochromatin components in Drosophila (James and Elgin, 54 1986).…”