A c-Myb mutant causes deregulated differentiation due to impaired histone binding and abrogated pioneer factor function.

ABSTRACT: The transcription factor c-Myb is involved in early differentiation and proliferation of haematopoietic cells, where it operates as a regulator of self-renewal and multi-lineage differentiation. Deregulated c-Myb plays critical roles in leukaemias and other human cancers. Due to its role as a master regulator, we hypothesized it might function as a pioneer transcription factor. Our approach to test this was to analyse a mutant of c-Myb, D152V, previously reported to cause haematopoietic defects in mice by an unknown mechanism. Our transcriptome data from K562 cells indicates that this mutation specifically affects c-Myb's ability to regulate genes involved in differentiation, causing failure in c-Myb's ability to block differentiation. Furthermore, we see a major effect of this mutation in

SUBMITTER: Fuglerud BM 

PROVIDER: S-EPMC5570105 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature