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Article
Open AccessPredicting gene expression state and prioritizing putative enhancers using 5hmC signal
Like its parent base 5-methylcytosine (5mC), 5-hydroxymethylcytosine (5hmC) is a direct epigenetic modification of cytosines in the context of CpG dinucleotides. 5hmC is the most abundant oxidized form of 5mC,...
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Article
Addressing Perinatal Opioid Use at a Local Health Department in Florida
Perinatal substance use disorders (SUDs) remain an urgent public health concern in the United States and are associated with increased maternal and infant morbidity and mortality. Establishing holistic prenata...
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Article
Open AccessAcute deletion of TET enzymes results in aneuploidy in mouse embryonic stem cells through decreased expression of Khdc3
TET (Ten-Eleven Translocation) dioxygenases effect DNA demethylation through successive oxidation of the methyl group of 5-methylcytosine (5mC) in DNA. In humans and in mouse models, TET loss-of-function has b...
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Article
TET deficiency perturbs mature B cell homeostasis and promotes oncogenesis associated with accumulation of G-quadruplex and R-loop structures
Enzymes of the TET family are methylcytosine dioxygenases that undergo frequent mutational or functional inactivation in human cancers. Recurrent loss-of-function mutations in TET proteins are frequent in huma...
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Article
Nano-optogenetic engineering of CAR T cells for precision immunotherapy with enhanced safety
Chimeric antigen receptor (CAR) T cell-based immunotherapy, approved by the US Food and Drug Administration, has shown curative potential in patients with haematological malignancies. However, owing to the lac...
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Article
BATF and IRF4 cooperate to counter exhaustion in tumor-infiltrating CAR T cells
The transcription factors nuclear factor of activated T cells (NFAT) and activator protein 1 (AP-1; Fos–Jun) cooperate to promote the effector functions of T cells, but NFAT in the absence of AP-1 imposes a ne...
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Article
Open AccessRoles of TET and TDG in DNA demethylation in proliferating and non-proliferating immune cells
TET enzymes mediate DNA demethylation by oxidizing 5-methylcytosine (5mC) in DNA to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC). Since these oxidized methylcytosines (...
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Article
Scientific divagations: from signaling and transcription to chromatin changes in T cells
Anjana Rao describes the team effort to define the changes in chromatin accessibility in naive T cells during TH1 and TH2 cell differentiation after stimulation with TCR ligands and the appropriate cytokines. Her...
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Article
DNMT3A and TET2 mutations reshape hematopoiesis in opposing ways
TET2 and DNMT3A mutations lead to similar long-term outcomes in blood cancers despite the antagonistic biochemical functions of their encoded proteins. A new study highlights the opposing effects of TET2 and DNMT...
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Article
An in vivo genome-wide CRISPR screen identifies the RNA-binding protein Staufen2 as a key regulator of myeloid leukemia
Aggressive myeloid leukemias such as blast crisis chronic myeloid leukemia and acute myeloid leukemia remain highly lethal. Here we report a genome-wide in vivo CRISPR screen to identify new dependencies in th...
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Article
TET methylcytosine oxidases: new insights from a decade of research
In mammals, DNA methyltransferases transfer a methyl group from S-adenosylmethionine to the 5 position of cytosine in DNA. The product of this reaction, 5-methylcytosine (5mC), has many roles, particularly in ...
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Article
Defining ‘T cell exhaustion’
‘T cell exhaustion’ is a broad term that has been used to describe the response of T cells to chronic antigen stimulation, first in the setting of chronic viral infection but more recently in response to tumou...
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Article
Structural basis of HMCES interactions with abasic DNA and multivalent substrate recognition
Embryonic stem cell-specific 5-hydroxymethylcytosine-binding protein (HMCES) can covalently cross-link to abasic sites in single-stranded DNA at stalled replication forks to prevent genome instability. Here, w...
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Article
Open AccessLoss of TET2 and TET3 in regulatory T cells unleashes effector function
TET enzymes oxidize 5-methylcytosine to 5-hydroxymethylcytosine and other oxidized methylcytosines in DNA. Here we examine the role of TET proteins in regulatory T (Treg) cells. Tet2/3fl/flFoxp3Cre mice lacking T...
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Article
NR4A transcription factors limit CAR T cell function in solid tumours
T cells expressing chimeric antigen receptors (CAR T cells) targeting human CD19 (hCD19) have shown clinical efficacy against B cell malignancies1,2. CAR T cells have been less effective against solid tumours3–5,...
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Article
YAP and MRTF-A, transcriptional co-activators of RhoA-mediated gene expression, are critical for glioblastoma tumorigenicity
The role of YAP (Yes-associated protein 1) and MRTF-A (myocardin-related transcription factor A), two transcriptional co-activators regulated downstream of GPCRs (G protein-coupled receptors) and RhoA, in the ...
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Article
Open AccessTCR signal strength controls thymic differentiation of iNKT cell subsets
During development in the thymus, invariant natural killer T (iNKT) cells commit to one of three major functionally different subsets, iNKT1, iNKT2, and iNKT17. Here, we show that T cell antigen receptor (TCR)...
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Article
Open AccessNFAT2 is a critical regulator of the anergic phenotype in chronic lymphocytic leukaemia
Chronic lymphocytic leukaemia (CLL) is a clonal disorder of mature B cells. Most patients are characterised by an indolent disease course and an anergic phenotype of their leukaemia cells, which refers to a st...
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Article
Erratum: The microRNA miR-31 inhibits CD8+ T cell function in chronic viral infection
Nat. Immunol.; doi:10.1038/ni.3755; corrected online 2 June 2017 In the version of this article initially published online, the symbols in the key for Figure 2a were reversed. The correct key symbol colors are...
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Article
The microRNA miR-31 inhibits CD8+ T cell function in chronic viral infection
Wucherpfennig and colleagues show that the microRNA miR-31 increases the sensitivity of T cells to type I interferons, which interferes with effector T cell function during chronic infection.