The polycomb repressive complex 2 governs life and death of peripheral T cells

Zhang, Yuxia; Kinkel, Sarah; Maksimovic, Jovana; Bandala‐Sanchez, Esther; Tanzer, Maria C.; Naselli, Gaetano; Zhang, Jianguo; Zhan, Yifan; Lew, Andrew M.; Silke, John; Oshlack, Alicia; Blewitt, Marnie E.; Harrison, Leonard C.

doi:10.1182/blood-2013-12-544106

Cited by 98 publications

(127 citation statements)

References 55 publications

(64 reference statements)

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“…During in vitro polarization, the activity of EZH2 also prevents plasticity between T H 1 and T H 2 cell subsets and supports pT Reg cell generation by inhibiting IFNγ expression 153,154 . However, T H 17 cell polarization seems to be impaired by increased PRC2 activity 154,155 . Interestingly, in cells lacking H3K27 KDM JMJD3 (also known as KDM6B), T H 17 cell polarization is enhanced, and many polarized T cell subsets exhibit enhanced stability 156 .…”

Section: Inhibiting Dna Accessibility With Heterochromatinmentioning

confidence: 99%

Harnessing the plasticity of CD4+ T cells to treat immune-mediated disease

2016

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| CD4 + T cells differentiate and acquire distinct functions to combat specific pathogens but can also adapt their functions in response to changing circumstances. Although this phenotypic plasticity can be potentially deleterious, driving immune pathology, it also provides important benefits that have led to its evolutionary preservation. Here, we review CD4 + T cell plasticity by examining the molecular mechanisms that regulate it -from the extracellular cues that initiate and drive cells towards varying phenotypes, to the cytosolic signalling cascades that decipher these cues and transmit them into the cell and to the nucleus, where these signals imprint specific gene expression programmes. By understanding how this functional flexibility is achieved, we may open doors to new therapeutic approaches that harness this property of T cells.

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Section: Inhibiting Dna Accessibility With Heterochromatinmentioning

confidence: 99%

Harnessing the plasticity of CD4+ T cells to treat immune-mediated disease

2016

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“…In addition to HSC regulation, PRC2 also has an essential role in lymphoid development. Conditional deletion of EZH2 in the lymphoid lineage revealed its crucial role in early B-cell development, rearrangement of the Igh gene, germinal center formation, and differentiation and survival of CD4 + T help1 (Th1) and Th2 cells (Su et al 2003;Beguelin et al 2013;Caganova et al 2013;Tumes et al 2013;Zhang et al 2014). Similarly, Suz12 deficiency causes severe defects in B and T lymphopoiesis .…”

Section: Polycomb Group (Pcg) Proteins In Normal and Malignant Hematomentioning

confidence: 99%

Epigenetics of hematopoiesis and hematological malignancies

Hu¹,

Shilatifard

2016

Genes Dev.

128

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Hematological malignancies comprise a diverse set of lymphoid and myeloid neoplasms in which normal hematopoiesis has gone awry and together account for ∼10% of all new cancer cases diagnosed in the United States in 2016. Recent intensive genomic sequencing of hematopoietic malignancies has identified recurrent mutations in genes that encode regulators of chromatin structure and function, highlighting the central role that aberrant epigenetic regulation plays in the pathogenesis of these neoplasms. Deciphering the molecular mechanisms for how alterations in epigenetic modifiers, specifically histone and DNA methylases and demethylases, drive hematopoietic cancer could provide new avenues for developing novel targeted epigenetic therapies for treating hematological malignancies. Just as past studies of blood cancers led to pioneering discoveries relevant to other cancers, determining the contribution of epigenetic modifiers in hematologic cancers could also have a broader impact on our understanding of the pathogenesis of solid tumors in which these factors are mutated.

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“…1 T-cells, 22 but it was largely dispensable for T-lymphoid development in the thymus. 23 Although several studies have shown that conditional inactivation of Ezh2 appears to have minimal impact on HSC function in adult mice, the role of Ezh2 in fetal hematopoiesis is less clear.…”

Section: Introductionmentioning

confidence: 99%

“…Indeed, a spectrum of mutations in EED, EZH2, and SUZ12 has been described in many human cancers including lymphoid and myeloid malignancies, highlighting the association of altered PRC2 activity with oncogenesis. 22,[30][31][32][33][34][35] Thus, although PRC2 has become a compelling therapeutic target in malignancy, a more detailed understanding of the complex functional consequences of altered PRC2 activity in the hematopoietic system will be a prerequisite for effective manipulation of PRC2 activity in disease.…”

Section: Introductionmentioning

confidence: 99%