IMR Press / FBS / Volume 16 / Issue 2 / DOI: 10.31083/j.fbs1602010
Open Access Review
Transcriptional Regulation of the Lineage-Determining Gene PU.1 in Normal and Malignant Hematopoiesis: Current Understanding and Therapeutic Perspective
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1 Department of Pathology, University of Virginia School of Medicine, Charlottesville, VA 22908, USA
2 Cancer Science Institute, National University of Singapore, 117599 Singapore, Singapore
3 Harvard Stem Cell Institute, Harvard Medical School, Boston, MA 02115, USA
4 Molecular Genetics & Epigenetics Program, University of Virginia Comprehensive Cancer Center, Charlottesville, VA 22908, USA
*Correspondence: bontrinh@virginia.edu (Bon Q. Trinh)
These authors contributed equally.
§These authors contributed equally.
Front. Biosci. (Schol Ed) 2024, 16(2), 10; https://doi.org/10.31083/j.fbs1602010
Submitted: 5 January 2024 | Revised: 5 March 2024 | Accepted: 28 March 2024 | Published: 6 May 2024
Copyright: © 2024 The Author(s). Published by IMR Press.
This is an open access article under the CC BY 4.0 license.
Abstract

The ETS transcription factor PU.1 plays an essential role in blood cell development. Its precise expression pattern is governed by cis-regulatory 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.

Keywords
chromatin signature
enhancer
silencer
cis-regulatory elements
ncRNAs
AML
myeloid development
Funding
1P01HL131477-6 A1/National Heart, Lung, and Blood Institute
NCI K01 CA222707/National Cancer Institute
134088-IRG-19-143-33-IRG/American Cancer Society
Figures
Fig. 1.
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