Language
English
Publication Date
12-16-2024
Journal
Cancer Research
DOI
10.1158/0008-5472.CAN-24-3957
PMID
39476188
PMCID
PMC11866459
PubMedCentral® Posted Date
12-16-2025
PubMedCentral® Full Text Version
Author MSS
Abstract
Cancers frequently co-opt lineage-specific transcription factors (TF) utilized in normal development to sustain proliferation. However, the effects of these TFs on tumor development depend considerably on where in the genome they bind. A new article by Taylor and colleagues expands on previously developed diamidine compounds that obstruct the DNA binding sites of the pioneer TF PU.1 (SPI1) in acute myeloid leukemia. Immobilization and sequencing of genomic DNA targeted by these compounds revealed that these inhibitors alter the genomic binding patterns of PU.1. The authors report that their strategy constrains the genomic binding preferences of PU.1, leading to redistribution of PU.1 to promoters and other gene-proximal regions with elevated guanine/cytosine content. In this study, we discuss recent developments for targeting PU.1 in hematologic malignancies. We also explore the shared functional roles of PU.1 and SWI/SNF ATP-dependent chromatin remodeling complexes, which not only work together to sustain the enhancer landscape needed for tumor cell proliferation but also play key roles in nontumor settings.
Keywords
Humans, Trans-Activators, Proto-Oncogene Proteins, Transcription Factors, Animals, Leukemia, Myeloid, Acute, Chromatin Assembly and Disassembly, Antineoplastic Agents
Published Open-Access
yes
Recommended Citation
Katerina Cermakova and H Courtney Hodges, "Pharmacologic Blockade of a Pioneer Transcription Factor" (2024). Faculty, Staff and Students Publications. 6393.
https://digitalcommons.library.tmc.edu/baylor_docs/6393