Transcriptional regulation of haematopoietic transcription factors

The control of differential gene expression is central to all metazoan biology. Haematopoiesis represents one of the best understood developmental systems where multipotent blood stem cells give rise to a range of phenotypically distinct mature cell types, all characterised by their own distinctive gene expression profiles. Small combinations of lineage-determining transcription factors drive the development of specific mature lineages from multipotent precursors. Given their powerful regulatory nature, it is imperative that the expression of these lineage-determining transcription factors is under tight control, a fact underlined by the observation that their misexpression commonly leads to the development of leukaemia. Here we review recent studies on the transcriptional control of key haematopoietic transcription factors, which demonstrate that gene loci contain multiple modular regulatory regions within which specific regulatory codes can be identified, that some modular elements cooperate to mediate appropriate tissue-specific expression, and that long-range approaches will be necessary to capture all relevant regulatory elements. We also explore how changes in technology will impact on this area of research in the future.