The homeobox genes encode a family of transcription factors that regulate development and postnatal tissue homeostasis. Encoded by the HOXB4 gene, the nuclear phosphoprotein HoxB4 plays a key role in regulating the balance between hematopoietic stem cell renewal and differentiation. Hematopoietic expression of HoxB4 is regulated by the binding of USF-1 and USF-2, the binding of which may be favored by cytokines promoting stem cell self-renewal versus differentiation. HoxB4 is dependent on AP-1 expression to induce changes in cellular proliferation and differentiation, which increases the levels of cyclin D1, thereby linking HoxB4 with key elements of the cell cycle machinery. HoxB4 also participates in the downregulation of c-Myc expression. It is expressed in developing hair follicles as well as in K-562 and HL-60 cells.