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CUT&RUN comparing occupancy of MAX, MNT, MYC in MAX WT and KO B220+ cells

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE132967 | GEO | 2019/06/20

REPOSITORIES: GEO

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