Control of Foxp3 induction and maintenance by sequential histone acetylation and DNA demethylation.

Regulatory T (T) cells play crucial roles in suppressing deleterious immune response. Here, we investigate how T cells are mechanistically induced in vitro (iT) and stabilized via transcriptional regulation of T lineage-specifying factor Foxp3. We find that acetylation of histone tails at the Foxp3 promoter is required for inducing Foxp3 transcription.

Combinatorial ETS1-dependent control of oncogenic NOTCH1 enhancers in T-cell leukemia.

Notch activation is highly prevalent among cancers, in particular T-cell acute lymphoblastic leukemia (T-ALL). However, the use of pan-Notch inhibitors to treat cancers has been hampered by adverse effects, particularly intestinal toxicities. To circumvent this barrier in T-ALL, we aimed to inhibit ETS1, a developmentally important T-cell transcription factor previously shown to co-bind Notch response elements.

Stage-specific roles for Zmiz1 in Notch-dependent steps of early T-cell development.

Notch1 signaling must elevate to high levels in order to drive the proliferation of CD4CD8 double-negative (DN) thymocytes and progression to the CD4CD8 double-positive (DP) stage through β-selection. During this critical phase of pre-T-cell development, which is also known as the DN-DP transition, it is unclear whether the Notch1 transcriptional complex strengthens its signal output as a discrete unit or through cofactors. We previously showed that the protein inhibitor of activated STAT-like coactivator Zmiz1 is a context-dependent cofactor of Notch1 in T-cell leukemia.