Abstract
The human myeloid leukemia cell line HL-60 differentiate into monocytes following treatment with 12-O-tetradecanoylphorbol-13-acetate (TPA). However, the mechanism underlying the differentiation of these cells in response to TPA has not been fully elucidated. In this study, we performed ChIP-seq profiling of RNA Pol II, HDAC2, Acetyl H3 (AcH3), and H3K27me3 and analyzed differential chromatin state changes during TPA-induced differentiation of HL-60 cells. We focused on atypically active genes, which showed enhanced H3 acetylation despite increased HDAC2 recruitment. We found that HDAC2 positively regulates the expression of these genes in a histone deacetylase activity-independent manner. HDAC2 interacted with and recruited paired box 5 (PAX5) to the promoters of the target genes and regulated HL-60 cell differentiation by PAX5-mediated gene activation. Taken together, these data elucidated the specific-chromatin status during HL-60 cell differentiation following TPA exposure and suggested that HDAC2 can activate transcription of certain genes through interactions with PAX5 in a deacetylase activity-independent pathway.
Highlights
Acute myeloid leukemia (AML) is a type of cancer that occurs in the bone marrow, blood, and other tissues of the hematopoietic system
We found that the enrichment levels of Acetyl H3 (AcH3), RNA Pol II, HDAC2, and H3K27me3 were significantly increased in the TPA-treated cells compared to those in the controls (Fig 1A)
The second group was associated with atypically active genes, which were characterized by the presence of HDAC2 as well as AcH3 and RNA Pol II
Summary
Acute myeloid leukemia (AML) is a type of cancer that occurs in the bone marrow, blood, and other tissues of the hematopoietic system. The average age of AML patients is approximately 68 years, and most of these patients cannot be treated with intensive chemotherapy because of the unexpected side effects and toxicity of the chemotherapeutic agents [2]. For this reason, understanding the mechanisms underlying the action of these agents is indispensable for their application to patients. HL-60 cells, a human AML cell line, are great models to study the properties of leukemia cells and to test chemotherapeutic agents. They have the ability to differentiate into granulocytes, monocytes, macrophage, and eosinophils following induction by various chemicals [3].
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