Mercoledì 13 Marzo 2024,
ore 13 Edificio Asclepio U8-Aula 8
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How gene expression is controlled to preserve human T-cell quiescence is poorly understood. We have recently discovered that non-canonical splicing variants containing LINE1 transposable elements enforce naïve CD4+ T-cell quiescence. LINE1-transcripts derive from CD4+-specific genes upregulated during T-cell activation. In naïve CD4+ T-cells, LINE1-transcripts are kept at chromatin by Nucleolin; they act in cis stalling gene expression, with a still uncovered epigenetic mechanism. Preliminary evidence suggest that LINE1-transcripts form a complex with Nucleolin and KAP1 that organize open chromatin compartments via phase separation.
T-cell activation induces LINE1-transcript downregulation by PTBP1 splicing suppressor and promotes expression of the corresponding protein-coding genes through mTORC1. Dysfunctional T-cells, exhausted in vitro or tumor-infiltrating lymphocytes (TILs), accumulate LINE1-transcripts at chromatin. Remarkably, depletion of LINE1-transcripts restores TIL effector function (Marasca F. et al, Nature Genetics, 2022).
We introduce LINE1-transcripts as the first of a new class of epigenetic immunoregulatory molecules that enforce quiescence of naïve T lymphocytes controlling chromatin organization and thus the expression of fundamental genes for T-cell function. Besides, the discovery that LINE1-transcripts can reaccumulate in the nuclei of different pathological contexts such as tumor microenvironment suggests that they could represent a novel checkpoint that regulate the switch from quiescence to activation and dysfunction.
Host: Prof.ssa Angela Bentivegna
Beatrice Bodega
Beatrice Bodega graduated in Medical Biotechnology in 2003 and obtained a PhD in Biotechnology Applied to Medical Sciences at in 2006 at University of Milan.
She then moved to Rome in 2009 in the laboratory of Valerio Orlando (Dulbecco Telethon Institute at the Santa Lucia Foundation) to specialize in epigenetics and in investigating the role of transposable elements (LINE1) in human cell differentiation.
In 2014, she started her independent career as Group Leader at INGM. Since 2021 she is Associate Professor of Molecular Biology at University of Milan.
Since 20 years she has been interested in understanding the molecular function of non-coding DNA, in particular in the modulation of cellular processes (i.e. differentiation, homeostasis, plasticity) and how this portion of the genome modulates the response to the environment, the adaptation and progression of human diseases. Her laboratory combines molecular, genomic and advanced imaging approaches with computational biology to describe the molecular mechanisms of DNA repetitive sequences, particularly the Transposable Elements, in human biology with a strong focus on translational aspects in biomedical research.