학술논문
Suv39h-catalyzed H3K9me3 is critical for euchromatic genome organization and the maintenance of gene transcription.
Document Type
Academic Journal
Author
Keenan CR; The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, 3052, Australia; keenanc@unimelb.edu.au rallan@wehi.edu.au.; Department of Medical Biology, The University of Melbourne, Parkville, Victoria, 3010, Australia.; Coughlan HD; The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, 3052, Australia.; Department of Medical Biology, The University of Melbourne, Parkville, Victoria, 3010, Australia.; Iannarella N; The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, 3052, Australia.; Tapia Del Fierro A; The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, 3052, Australia.; Department of Medical Biology, The University of Melbourne, Parkville, Victoria, 3010, Australia.; Keniry A; The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, 3052, Australia.; Department of Medical Biology, The University of Melbourne, Parkville, Victoria, 3010, Australia.; Johanson TM; The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, 3052, Australia.; Department of Medical Biology, The University of Melbourne, Parkville, Victoria, 3010, Australia.; Chan WF; The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, 3052, Australia.; Department of Medical Biology, The University of Melbourne, Parkville, Victoria, 3010, Australia.; Garnham AL; The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, 3052, Australia.; Department of Medical Biology, The University of Melbourne, Parkville, Victoria, 3010, Australia.; Whitehead LW; The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, 3052, Australia.; Department of Medical Biology, The University of Melbourne, Parkville, Victoria, 3010, Australia.; Blewitt ME; The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, 3052, Australia.; Department of Medical Biology, The University of Melbourne, Parkville, Victoria, 3010, Australia.; Smyth GK; The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, 3052, Australia.; School of Mathematics and Statistics, The University of Melbourne, Parkville, Victoria, 3010, Australia.; Allan RS; The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, 3052, Australia; keenanc@unimelb.edu.au rallan@wehi.edu.au.; Department of Medical Biology, The University of Melbourne, Parkville, Victoria, 3010, Australia.
Source
Publisher: Cold Spring Harbor Laboratory Press Country of Publication: United States NLM ID: 9518021 Publication Model: Electronic Cited Medium: Internet ISSN: 1549-5469 (Electronic) Linking ISSN: 10889051 NLM ISO Abbreviation: Genome Res Subsets: MEDLINE
Subject
Language
English
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.
(© 2024 Keenan et al.; Published by Cold Spring Harbor Laboratory Press.)
(© 2024 Keenan et al.; Published by Cold Spring Harbor Laboratory Press.)