Deacetylase activity-independent transcriptional activation by HDAC2 during TPA-induced HL-60 cell differentiation.
Hyeonsoo JungJi-Young KimKee-Beom KimYun-Cheol ChaeYoonsoo HahnJung-Woong KimSang Beom SeoPublished in: PloS one (2018)
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.
Keyphrases
- histone deacetylase
- genome wide
- transcription factor
- genome wide identification
- induced apoptosis
- dna methylation
- gene expression
- cell cycle arrest
- high glucose
- copy number
- endothelial cells
- dna damage
- bioinformatics analysis
- dendritic cells
- single cell
- high throughput
- genome wide analysis
- acute myeloid leukemia
- poor prognosis
- drug induced
- oxidative stress
- cell death
- binding protein
- signaling pathway
- immune response
- circulating tumor cells
- heat stress
- heat shock
- deep learning
- rna seq
- replacement therapy