The Univeristy of Melbourne The Royal Melbourne Hopspital

A joint venture between The University of Melbourne and The Royal Melbourne Hospital

Publication

Active maintenance of CD8+ T cell naivety through regulation of global genome architecture


Authors:

  • Russ, Brendan E.
  • Barugahare, Adele
  • Dakle, Pushkar
  • Tsyganov, Kirril
  • Quon, Sara
  • Yu, Bingfei
  • Li, Jasmine
  • Lee, Jason K.C.
  • Olshansky, Moshe
  • He, Zhaohren
  • Harrison, Paul F.
  • See, Michael
  • Nussing, Simone
  • Morey, Alison E.
  • Udupa, Vibha A.
  • Bennett, Taylah J.
  • Kallies, Axel
  • Murre, Cornelis
  • Collas, Phillipe
  • Powell, David
  • Goldrath, Ananda W.
  • Turner, Stephen J.

Details:

Cell Reports, Volume 42, Issue 10, 2023-10-31

Article Link: Click here

The differentiation of naive CD8+ T lymphocytes into cytotoxic effector and memory CTL results in large-scale changes in transcriptional and phenotypic profiles. Little is known about how large-scale changes in genome organization underpin these transcriptional programs. We use Hi-C to map changes in the spatial organization of long-range genome contacts within naive, effector, and memory virus-specific CD8+ T cells. We observe that the architecture of the naive CD8+ T cell genome is distinct from effector and memory genome configurations, with extensive changes within discrete functional chromatin domains associated with effector/memory differentiation. Deletion of BACH2, or to a lesser extent, reducing SATB1 DNA binding, within naive CD8+ T cells results in a chromatin architecture more reminiscent of effector/memory states. This suggests that key transcription factors within naive CD8+ T cells act to restrain T cell differentiation by actively enforcing a unique naive chromatin state.