Transcriptional regulation of BHLHB2 induced by PML-RARα / 中国实验血液学杂志

ABSTRACT

Objective of this study was to investigate the transcriptional regulation of BHLHB2 gene by the PML-RARα fusion protein in APL cells and reveal the pathogenesis of APL. RT-PCR was performed to detect the expression change of BHLHB2 before and after the induction of PML-RARα in PR9 cells, and its expression level after the treatment of ATRA in PR9 and APL patient derived NB4 cells. Chromatin immunoprecipitation (ChIP)-based PCR was used to analyze whether the BHLHB2 promoter could be bound by PML-RARα in vivo. A large-scale gene expression profile dataset was used to observe the expression pattern of BHLHB2 in AML. The results showed that the expression level of BHLHB2 was significantly reduced with the induction of PML-RARα and ATRA could reverse this inhibition in both PR9 and NB4 cells and increase the expression of BHLHB2. However, the expression of BHLHB2 could not be induced by ATRA in U937 cells which do not express PML-RARα. Mechanism study revealed that PML-RARα could bound to the promoter of BHLHB2 in vivo to regulate the the expression of BHLHB2. It was found that the expression of BHLHB2 was relatively lower in APL as compared with other subtypes of AML and normal bone marrow cells. It is concluded that BHLHB2 is the target of PML-RARα, and the expression of BHLHB2 is inhibited by PML-RARα through binding to its promoter in APL.