Dissertation/Thesis Abstract

PRC2-Mediated H3K27me3 Repression Promotes Effector CD8 + T Cell Terminal Differentiation and Loss of Multipotency
by Gray, Simon Matthew, Ph.D., Yale University, 2016, 154; 10584947
Abstract (Summary)

Elucidating how multipotent memory precursor (MP) cells maintain developmental plasticity and longevity to provide long-term immunity while most effector cells develop into terminally differentiated effector (TE) cells with limited survival is necessary for understanding immunological memory formation. We profiled active (H3K27Ac) and repressed (H3K27me3) chromatin states in naïve, MP and TE CD8+ T cells during viral infection, and observed increased H3K27me3 at numerous pro-memory and pro-survival genes in TE relative to MP cells, indicative of fate restriction, but permissive chromatin at both pro-memory and pro-effector genes in MP cells, indicative of multipotency. Deficiency in PRC2-mediated H3K27me3 deposition impaired clonal expansion and TE cell differentiation, but minimally impacted memory cell maturation. Abundant H3K27me3 deposition at pro-memory genes occurred relatively late during TE cell development in a FOXO1-regulated manner. These results outline a detailed temporal model for how effector T cells lose memory cell potential through selective epigenetic-silencing of pro-memory genes.

Indexing (document details)
Advisor: Kaech, Susan
Commitee:
School: Yale University
School Location: United States -- Connecticut
Source: DAI-B 78/07(E), Dissertation Abstracts International
Source Type: DISSERTATION
Subjects: Immunology
Keywords: CD8+ T Cell, Differentiation, EZH2, Epigenetics, H3K27me3, Polycomb
Publication Number: 10584947
ISBN: 9781369635348
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