Identification of ZNF384 as a regulator of epigenome in leukemia

Abstract

Leukemia is a complex hematologic cancer driven by genetic and epigenetic changes that impact gene expression. Understanding these molecular mechanisms is essential for improving leukemia diagnosis and prognosis. This study examines the role of the zinc finger protein ZNF384 in the epigenome and its influence on gene regulation in leukemia. We analyzed next-generation sequencing data from The Encyclopedia of DNA Elements (ENCODE), integrating datasets such as chromatin immunoprecipitation sequencing (ChIP-seq) of ZNF384 and regulatory histone marks, RNA sequencing (RNA-seq), and Hi-C data from K562 and GM12878 cells. Additionally, we used RNA-seq from K562 ZNF384 knock-down (KD) cells generated via CRISPR interference (CRISPRi) to validate our findings. This enabled us to explore the chromatin interaction patterns of ZNF384 and its regulatory impact. Our results demonstrate that ZNF384 associates with promoters and enhancers in K562 and GM12878 cells, facilitating increased transcription levels. We also found ZNF384 enriched at topologically associating domain (TAD) boundaries and chromatin loops, suggesting a role in three-dimensional (3D) chromatin organization. Furthermore, we identified a significant binding of ZNF384 at SINE-Alu elements in both K562 and GM12878 cells. In summary, this study highlights the regulatory role of ZNF384 in the leukemia epigenome and its impact on gene expression. Understanding the oncogenic implications of ZNF384 may improve leukemia diagnosis and prognosis.