Beatrice Bodega, PhD - "Transcription and dynamics of Transposable Elements keeps on fire the genome of human T lymphocytes"

  • When Jul 19, 2022 from 12:00 PM to 01:15 PM (Europe/Berlin / UTC200)
  • Where Tigem Auditorium Vesuvius
  • Contact Name
  • Contact Phone 08119230659
  • Add event to calendar iCal

BB (1).jpegBeatrice Bodega, PhD
INGM, Istituto Nazionale di Genetica Molecolare, Milan, Italy
Department of Biosciences, University of Milan, Milan, Italy

Short CV

How gene expression is controlled to preserve human T-cell quiescence is poorly understood. We discovered that LINE1 transposable elements are spliced in novel transcripts to enforce naïve T-cell quiescence. LINE1-transcripts derive from CD4+-specific genes upregulated during T-cell activation. In naïve CD4+ T-cells, LINE1-transcripts are regulated by the transcription factor IRF4 and kept at chromatin by Nucleolin; they act in cis, hampering H3K36me3 levels and stalling gene expression. T-cell differentiation induces LINE1-transcript downregulation by PTBP1 splicing suppressor and promotes expression of the corresponding protein-coding genes by GTF2F1 elongating factor through mTORC1. Dysfunctional T-cells, exhausted in vitro or tumor-infiltrating lymphocytes, accumulate LINE1-transcripts at chromatin. Remarkably, depletion of LINE1-transcripts restores TIL effector function.
We introduce LINE1-transcripts as the first of a new class of epigenetic immunoregulatory molecules that enforce the quiescence of naïve T lymphocytes controlling chromatin organization and thus the expression of fundamental genes for T-cell function.