Heat Stress Affects H3K9me3 Level at Human Alpha Satellite DNA Repeats

Abstract

Satellite DNAs are tandemly repeated sequences preferentially assembled into large arrays within constitutive heterochromatin and their transcription is often activated by stress conditions, particularly by heat stress. Bioinformatic analyses of sequenced genomes however reveal single repeats or short arrays of satellite DNAs dispersed in the vicinity of genes within euchromatin. Here, we analyze transcription of a major human alpha satellite DNA upon heat stress and follow the dynamics of “silent” H3K9me3 and “active” H3K4me2/3 histone marks at dispersed euchromatic and tandemly arranged heterochromatic alpha repeats. The results show H3K9me3 enrichment at alpha repeats upon heat stress, which correlates with the dynamics of alpha satellite DNA transcription activation, while no change in H3K4me2/3 level is detected. Spreading of H3K9me3 up to 1–2 kb from the insertion sites of the euchromatic alpha repeats is detected, revealing the alpha repeats as modulators of local chromatin structure. In addition, expression of genes containing alpha repeats within introns as well as of genes closest to the intergenic alpha repeats is downregulated upon heat stress. Further studies are necessary to reveal the possible contribution of H3K9me3 enriched alpha repeats, in particular those located within introns, to the silencing of their associated genes.

Evolutionary History of Alpha Satellite DNA Repeats Dispersed within Human Genome Euchromatin

“…Considering the influence of dispersed satellite repeats on local chromatin structure and gene expression in different organisms ( Feliciello, Akrap, Ugarković 2015 ; Joshi and Meller 2017 ; Halbach et al. 2020 ; Feliciello et al. 2020 ), studies of their evolutionary dynamics and mechanisms of proliferation within euchromatin could contribute to the explanation of their potential role in the evolution of gene regulatory networks.…”

“…In addition to their (peri)centromeric location, a bioinformatic search of the human genome revealed the presence of 133 blocks of alpha satellite located >5 Mb from the centromere ( Rudd and Willard 2004 ). Heterochromatic and euchromatic alpha satellite DNA repeats are characterized by increased levels of H3K9me3 upon heat stress which can possibly affect neighboring gene expression ( Feliciello et al. 2020 ).…”

Distinct Regulation of the Expression of Satellite DNAs in the Beetle Tribolium castaneum

“…The influence of chromatin state on the expression of transposon-derived small RNAs during embryogenesis was reported in plants [ 34 ]. Heat stress was known to specifically affect heterochromatin by provoking its decondensation and decrease of nucleosome occupancy, resulting in transcription activation of heterochromatic satellite DNAs [ 35 , 36 , 37 , 38 , 39 ]. It is possible that heterochromatin dynamics during embryonic development and upon heat stress influences major TCAST1 satellite transcription, while the TCAST2 satellite transcription, proceeding predominantly from euchromatic clusters, is not significantly affected.…”

Stress as a Chromatin Landscape Architect

“…Hsp70 gene is one of the best-studied genes in terms of chromatin remodeling during transcriptional activation, and besides stress, a mood stabilizing and anticonvulsant drug, valproic acid, increases H3K4me2 of Hsp70 promoter and induces Hsp70 transcription in neurons ( Marinova et al, 2011 ). Additionally, a number of studies have detected HS- and HSF1-dependent activation of typically silent constitutive heterochromatin regions, the satellite repeats on human chromosome 9 ( Jolly et al, 2002 , 2004 ; Rizzi et al, 2003 ; Valgardsdottir et al, 2008 ; Sengupta et al, 2009 ; Eymery et al, 2010 ; Pezer and Ugarkovic, 2012 ; Feliciello et al, 2015 ; Col et al, 2017 ; Feliciello et al, 2020 ). These repeats are often closely associated with the nucleoli periphery, one of the major locations of heterochromatin domains within the nucleus ( Politz et al, 2016 ; Vertii et al, 2019 ; Bersaglieri et al, 2020 ; Bury et al, 2020 ; Wang et al, 2021 ).…”