Transcriptional Regulation of the Lineage-Determining Gene PU.1 in Normal and Malignant Hematopoiesis: Current Understanding and Therapeutic Perspective

Abstract

The ETS transcription factor PU.1 plays an essential role in blood cell development. Its precise expression pattern is governed by cisregulatory elements (CRE) acting at the chromatin level. CREs mediate the fine-tuning of graded levels of PU.1, deviations of which can cause acute myeloid leukemia. In this review, we perform an in-depth analysis of the regulation of PU.1 expression in normal and malignant hematopoiesis. We elaborate on the role of trans-acting factors and the biomolecular interplays in mediating local chromatin dynamics. Moreover, we discuss the current understanding of CRE bifunctionality exhibiting enhancer or silencer activities in different blood cell lineages and future directions toward gene-specific chromatin-targeted therapeutic development.