Suv39h-catalyzed H3K9me3 is critical for euchromatic genome organization and the maintenance of gene transcription

Keenan, CR; Coughlan, HD; Iannarella, N; Tapia Del Fierro, A; Keniry, A; Johanson, TM; Chan, WF; Garnham, AL; Whitehead, LW; Blewitt, ME; Smyth, GK; Allan, RS

Author(s): Keenan, CR; Coughlan, HD; Iannarella, N; Tapia Del Fierro, A; Keniry, A; Johanson, TM; Chan, WF; Garnham, AL; Whitehead, LW; Blewitt, ME; Smyth, GK; Allan, RS;
Details: Publication Year 2024-05-15,Volume 34,Issue #4,Page 556-571
Journal Title: Genome Research
Abstract: H3K9me3-dependent heterochromatin is critical for the silencing of repeat-rich pericentromeric regions and also has key roles in repressing lineage-inappropriate protein-coding genes in differentiation and development. Here, we investigate the molecular consequences of heterochromatin loss in cells deficient in both SUV39H1 and SUV39H2 (Suv39DKO), the major mammalian histone methyltransferase enzymes that catalyze heterochromatic H3K9me3 deposition. We reveal a paradoxical repression of protein-coding genes in Suv39DKO cells, with these differentially expressed genes principally in euchromatic (Tn5-accessible, H3K4me3- and H3K27ac-marked) rather than heterochromatic (H3K9me3-marked) or polycomb (H3K27me3-marked) regions. Examination of the three-dimensional (3D) nucleome reveals that transcriptomic dysregulation occurs in euchromatic regions close to the nuclear periphery in 3D space. Moreover, this transcriptomic dysregulation is highly correlated with altered 3D genome organization in Suv39DKO cells. Together, our results suggest that the nuclear lamina-tethering of Suv39-dependent H3K9me3 domains provides an essential scaffold to support euchromatic genome organization and the maintenance of gene transcription for healthy cellular function.
Publisher: CSHP
Keywords: *Euchromatin/metabolism/genetics; *Histones/metabolism/genetics; *Methyltransferases/metabolism/genetics; *Histone-Lysine N-Methyltransferase/metabolism/genetics; *Heterochromatin/metabolism/genetics; *Transcription, Genetic; *Repressor Proteins/metabolism/genetics; Animals; Mice; Humans; Gene Expression Regulation; Cell Line
Research Division(s): Immunology; Advanced Technology And Biology; Bioinformatics; Epigenetics And Development
PubMed ID: 38719473
Publisher's Version: https://doi.org/10.1101/gr.279119.124
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2024-05-20 07:53:37

Last Modified: 2024-05-20 10:11:57