c‐Maf interacts with c‐Myb to down‐regulate Bcl‐2 expression and increase apoptosis in peripheral CD4 cells

Abstract

The transcription factor c‐Maf is critical for IL‐4 production and the development of Th2 cells, which promote humoral immunity and protect against extracellular parasites. Yet, little else is known of c‐Maf function in CD4 cells. Here, we identify a novel role for c‐Maf in regulating susceptibility to apoptosis. Overexpression of c‐Maf results in increased susceptibility of CD4 cells to apoptosis induced by multiple stimuli, including growth factor withdrawal, dexamethasone, irradiation, and TCR engagement. This effect is independent of Fas or p53; however, Bcl‐2 expression is reduced in c‐Maf Tg CD4 cells. Immunoprecipitation and Western blot analyses demonstrate that c‐Maf–c‐Myb complex formation is enhanced among T cells from c‐Maf Tg mice compared to non‐Tg littermates following TCR engagement. Unlike non‐Tg T cells, c‐Myb binding to the Bcl‐2 promoter is not detectable in c‐Maf Tg T cells by chromatin immunoprecipitation. In reporter assays, Bcl‐2 promoter activity is reduced by c‐Maf in a dose‐dependent manner. Furthermore, transgene‐mediated Bcl‐2 expression corrects the apoptosis defect observed among c‐Maf Tg CD4 cells. These data suggest that c‐Maf can interact with c‐Myb to reduce Bcl‐2 expression, thereby limiting CD4 cell survival following TCR engagement.

Genome-Wide Identification of Human FOXP3 Target Genes in Natural Regulatory T Cells

“…The cooccurrence of these motifs is consistent with known roles for these transcription factors in nTregs (18,(65)(66)(67)(68)(69) and, in the case of AP-1, NFAT, and Runx family members, with their known physical interaction with FOXP3 (18,20,23). Several of the other transcription factor family motifs that are overrepresented in these sequences, such as BCL6 and PRDF, also contain members known to have a role in T cells, such as BCL6, PRDM1/Blimp-1, and cmyb (70)(71)(72)(73). The finding of potential PRDM1 motifs within FOXP3-bound regions is of particular interest given its relatively high level of expression in natural Tregs and its requirement for T cell homeostasis, nTreg function, and self-tolerance in the mouse (74,75), suggesting that FOXP3 and PRDM1 may cooperate to regulate gene expression in human Tregs.…”

MYBsuppresses differentiation and apoptosis of human breast cancer cells

“…To determine whether MYB acts directly on the BCL2 gene in breast cancer cells, we performed ChIP assays using MCF-7 cells. Potential MBS in BCL2 promoters 1 and 2 were identified based on binding sites previously mapped in other cell types [34,35] in conjunction with the established consensus sequence YAACN(G/T) for MYB protein binding [36,37]. Additional sites examined corresponded to those detected by ChIP-Seq in murine myeloid cells (Zhao et al , Defining the MYB Transcriptional Program by Genome-Wide Chromatin Occupancy and Expression Analyses, submitted), which are located within intron 2 and downstream of exon 3 (Figure 4c).…”

SUMO Conjugation Contributes to Immune Deviation in Nonobese Diabetic Mice by Suppressing c-Maf Transactivation of IL-4

“…CD4 cells were purified from spleen and lymph nodes pooled from 3–5 mice per strain as described previously (22). Purified CD4 cells were used immediately or activated with 5–10 μ g/ml plate-bound anti-CD3 (145-2C11; BD Pharmingen) and 1 μ g/ml soluble anti-CD28 (37.51; BD Pharmingen) for 8–36 h in RPMI 1640 (Invitrogen) plus 10% FBS (Atlanta Biologicals), 10 mM HEPES (Invitrogen), 50 μ M 2-ME, 2 mM glutamine, 100 U/ml penicillin, and 100 μ g/ml streptomycin (complete RPMI medium) before analysis.…”