Gene regulatory complexes: their role and regulation across normal and malignant hematopoiesis

Transcription is regulated in a multitude of ways to ensure lineage- and context-specific gene expression in a coordinated fashion. Hematopoiesis is an exemplary process for studying the mechanisms of tightly regulated activation and repression of gene expression programs through transcription and gene regulatory complexes. These complexes act by posttranslational modification of histones and nonhistone proteins, epigenetic modifications of DNA, ATP-dependent chromatin remodeling, scaffolding and recruitment of combinatorial protein complexes, and alteration of three-dimensional genome conformation to bring about lineage-specific gene expression. This review will focus on the function of these gene regulatory complexes in hematopoiesis and how they are hijacked in acute myeloid leukemia, highlighting therapeutic progress and opportunities.