Project description:The goal of this study was to genomic occupancy of MAX, MNT, MYC and E2F1 in B cells in the presence and absence of transcription factor MAX Although MAX is regarded as an obligate dimerization partner for MYC, its function in normal development and neoplasia is poorly defined. We show that B-cell specific deletion of Max has a modest effect on B-cell development but completely abrogates E -Myc driven lymphomagenesis. While Max loss only affects a few hundred genes in normal B cells, it leads to the global downregulation of Myc-activated genes in premalignant E -Myc cells. We show that the balance between MYC-MAX and MNT-MAX interactions in B cells shifts in pre-malignant B cells towards a MYC driven transcriptional program. Moreover, we find that MAX loss leads to a significant reduction in MYC protein levels and downregulation of direct transcriptional targets, including regulators of MYC stability. This phenomenon is also observed in multiple cell lines treated with MYC-MAX dimerization inhibitors. Our work uncovers a layer of Myc autoregulation critical for lymphomagenesis yet partly dispensable for normal development.
Project description:The goal of this study was to compare the genomic occupancy of MAX, MNT, MGA and RNA pol II Ser5 in MAX restored versus MAX null SCLC (mRPMaxKO)
Project description:Conventional crosslinked ChIP was performed on sgCtrl (control guide RNA) and sgMax (guide RNA against Max) transduced preSCs (early stage SCLC line). We find that loss of MAX leads to decreased MAX, MYC and MNT occupancy.
Project description:CUT&RUN comparing the occupancy of MAX, MNT, MGA, MYC and RNA pol II Ser5 in a MAX null vs MAX reconstituted mouse SCLC line (mRPMaxKO)
Project description:We generated mice null for MAX-like Protein X (MLX), encoded by Mlx. All male mice are sterile. We profiled testes tissue from WT versus KO mice by RNA-Seq. We performed ChIP-Seq on WT and KO testes for MLX and MAX, as well as ChIP-Seq for MLX and MAX from primary B220+ splenic B cells, and ChIP-Seq for MLX, MAX and MNT from 3T3 cell lines derived from WT and KO embryos.
Project description:The goal of this study was to compare expression profiles of B cells in the presence and absence of transcription factor MAX under normal and premalignant settings