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Extreme disruption of heterochromatin is required for accelerated hematopoietic aging.
Keenan, Christine R; Iannarella, Nadia; Naselli, Gaetano; Bediaga, Naiara G; Johanson, Timothy M; Harrison, Leonard C; Allan, Rhys S.
Afiliação
  • Keenan CR; The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia; and.
  • Iannarella N; Department of Medical Biology, The University of Melbourne, Parkville, VIC, Australia.
  • Naselli G; The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia; and.
  • Bediaga NG; The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia; and.
  • Johanson TM; The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia; and.
  • Harrison LC; Department of Medical Biology, The University of Melbourne, Parkville, VIC, Australia.
  • Allan RS; The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia; and.
Blood ; 135(23): 2049-2058, 2020 06 04.
Article em En | MEDLINE | ID: mdl-32305044
Loss of heterochromatin has been proposed as a universal mechanism of aging across different species and cell types. However, a comprehensive analysis of hematopoietic changes caused by heterochromatin loss is lacking. Moreover, there is conflict in the literature around the role of the major heterochromatic histone methyltransferase Suv39h1 in the aging process. Here, we use individual and dual deletion of Suv39h1 and Suv39h2 enzymes to examine the causal role of heterochromatin loss in hematopoietic cell development. Loss of neither Suv39h1 nor Suv39h2 individually had any effect on hematopoietic stem cell function or the development of mature lymphoid or myeloid lineages. However, deletion of both enzymes resulted in characteristic changes associated with aging such as reduced hematopoietic stem cell function, thymic involution and decreased lymphoid output with a skewing toward myeloid development, and increased memory T cells at the expense of naive T cells. These cellular changes were accompanied by molecular changes consistent with aging, including alterations in nuclear shape and increased nucleolar size. Together, our results indicate that the hematopoietic system has a remarkable tolerance for major disruptions in chromatin structure and reveal a role for Suv39h2 in depositing sufficient H3K9me3 to protect the entire hematopoietic system from changes associated with premature aging.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteínas Repressoras / Células-Tronco Hematopoéticas / Heterocromatina / Diferenciação Celular / Histona-Lisina N-Metiltransferase / Senilidade Prematura / Hematopoese / Metiltransferases Limite: Aged / Animals / Female / Humans / Male Idioma: En Revista: Blood Ano de publicação: 2020 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteínas Repressoras / Células-Tronco Hematopoéticas / Heterocromatina / Diferenciação Celular / Histona-Lisina N-Metiltransferase / Senilidade Prematura / Hematopoese / Metiltransferases Limite: Aged / Animals / Female / Humans / Male Idioma: En Revista: Blood Ano de publicação: 2020 Tipo de documento: Article