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Suv39h-catalyzed H3K9me3 is critical for euchromatic genome organization and the maintenance of gene transcription.
Keenan, Christine R; Coughlan, Hannah D; Iannarella, Nadia; Tapia Del Fierro, Andres; Keniry, Andrew; Johanson, Timothy M; Chan, Wing Fuk; Garnham, Alexandra L; Whitehead, Lachlan W; Blewitt, Marnie E; Smyth, Gordon K; Allan, Rhys S.
Afiliación
  • Keenan CR; The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, 3052, Australia; keenanc@unimelb.edu.au rallan@wehi.edu.au.
  • Coughlan HD; 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; 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.
  • Johanson TM; The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, 3052, Australia.
  • Chan WF; 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.
  • Whitehead LW; 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.
  • Smyth GK; Department of Medical Biology, The University of Melbourne, Parkville, Victoria, 3010, Australia.
  • Allan RS; The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, 3052, Australia.
Genome Res ; 34(4): 556-571, 2024 05 15.
Article en En | MEDLINE | ID: mdl-38719473
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.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Transcripción Genética / Heterocromatina / Histonas / N-Metiltransferasa de Histona-Lisina / Eucromatina / Metiltransferasas Límite: Animals Idioma: En Revista: Genome Res Asunto de la revista: BIOLOGIA MOLECULAR / GENETICA Año: 2024 Tipo del documento: Article

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Transcripción Genética / Heterocromatina / Histonas / N-Metiltransferasa de Histona-Lisina / Eucromatina / Metiltransferasas Límite: Animals Idioma: En Revista: Genome Res Asunto de la revista: BIOLOGIA MOLECULAR / GENETICA Año: 2024 Tipo del documento: Article