Epigenetic regulation of leukemogenesis and
leukemia cell differentiation
1. Genome-wide analysis to find histone modifications or interesting proteins involved in leukemia cell differentiation.
We found changes of epigenetic markers such as H3Ac, and H3K27me3 and modifier in TPA-mediated differentiation of HL-60 cell line. We identified regions with unconventional epigenetic patterns that positively correlate with HDAC and Ac-H3.
THP-1 differentiation affected recruitment of AcH3, RNA polII, HDAC2, and H3K27me3 to genome
2. Genome-wide analysis of before and after leukemia cell differentiation to understand leukemia differentiation pathway
We performed gene expression profiling in WHSC1 depleted K562 cells. We compared these data with that of hemin-mediated differentiation profiling data. In addition, we confirmed WHSC1 was reduced via proteosomal degradation in hemin proteasomal degradation in hemin-mediated differentiation.
Knockdown of WHSC1 induces gene expression involved in erythrocyte differentiation.
3. Global histone modifications to know gene expression, cell cycle and candidate genes involved in leukemia differentiation.
Differentiation of leukemia cell such as K562 and THP-1 affected global histone modifications. We found common change in H3S10 phosphorylation. Our previous study showed AURKA regulated H3S10 phosphorylation. Finally, we demonstrated that AURKA regulated leukemia cell differentiation.
Changes of global modifications in K562 and THP-1. Inhibition of AURKA induces leukemia cell differentiation.