Your browser doesn't support javascript.
loading
Heterochromatin formation and remodeling by IRTKS condensates counteract cellular senescence.
Xie, Jia; Lu, Zhao-Ning; Bai, Shi-Hao; Cui, Xiao-Fang; Lian, He-Yuan; Xie, Chen-Yi; Wang, Na; Wang, Lan; Han, Ze-Guang.
Afiliación
  • Xie J; Key Laboratory of Systems Biomedicine (Ministry of Education) and State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, 200240, China.
  • Lu ZN; Key Laboratory of Systems Biomedicine (Ministry of Education) and State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, 200240, China.
  • Bai SH; Key Laboratory of Systems Biomedicine (Ministry of Education) and State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, 200240, China.
  • Cui XF; Key Laboratory of Systems Biomedicine (Ministry of Education) and State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, 200240, China.
  • Lian HY; Key Laboratory of Systems Biomedicine (Ministry of Education) and State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, 200240, China.
  • Xie CY; Key Laboratory of Systems Biomedicine (Ministry of Education) and State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, 200240, China.
  • Wang N; Key Laboratory of Systems Biomedicine (Ministry of Education) and State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, 200240, China.
  • Wang L; Key Laboratory of Systems Biomedicine (Ministry of Education) and State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, 200240, China.
  • Han ZG; Key Laboratory of Systems Biomedicine (Ministry of Education) and State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, 200240, China. hanzg@sjtu.edu.cn.
EMBO J ; 43(20): 4542-4577, 2024 Oct.
Article en En | MEDLINE | ID: mdl-39192031
ABSTRACT
Heterochromatin, a key component of the eukaryotic nucleus, is fundamental to the regulation of genome stability, gene expression and cellular functions. However, the factors and mechanisms involved in heterochromatin formation and maintenance still remain largely unknown. Here, we show that insulin receptor tyrosine kinase substrate (IRTKS), an I-BAR domain protein, is indispensable for constitutive heterochromatin formation via liquid‒liquid phase separation (LLPS). In particular, IRTKS droplets can infiltrate heterochromatin condensates composed of HP1α and diverse DNA-bound nucleosomes. IRTKS can stabilize HP1α by recruiting the E2 ligase Ubc9 to SUMOylate HP1α, which enables it to form larger phase-separated droplets than unmodified HP1α. Furthermore, IRTKS deficiency leads to loss of heterochromatin, resulting in genome-wide changes in chromatin accessibility and aberrant transcription of repetitive DNA elements. This leads to activation of cGAS-STING pathway and type-I interferon (IFN-I) signaling, as well as to the induction of cellular senescence and senescence-associated secretory phenotype (SASP) responses. Collectively, our findings establish a mechanism by which IRTKS condensates consolidate constitutive heterochromatin, revealing an unexpected role of IRTKS as an epigenetic mediator of cellular senescence.
Asunto(s)
Palabras clave
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Heterocromatina / Senescencia Celular / Homólogo de la Proteína Chromobox 5 Límite: Animals / Humans Idioma: En Revista: EMBO J Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Heterocromatina / Senescencia Celular / Homólogo de la Proteína Chromobox 5 Límite: Animals / Humans Idioma: En Revista: EMBO J Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido