The online version of this article (doi:10.1186/s13045-016-0274-1) contains supplementary material, which is available to authorized users.
The authors declare that they have no competing interests.
SYW and KKW designed the study. SYW and XLW performed the experiments. MZ and SYW performed the analysis. KKW and SYW wrote the manuscript. KKW, SYW and YZL revised the manuscript. All authors read and approved the final manuscript.
Long noncoding RNA HOX antisense intergenic RNA myeloid 1 (HOTAIRM1) has been characterized as a critical factor in all-trans retinoic acid (ATRA)-induced differentiation of acute promyelocytic leukemia (APL) cells. However, the essential transcription factor for gene expression of HOTAIRM1 is still unknown.
Chromatin immunoprecipitation (ChIP) assays revealed that PU.1 constitutively bound to the regulatory region of HOTAIRM1. Co-expression of PU.1 led to the transactivation of the regulatory region of HOTAIRM1 in a reporter assay. Detailed analysis showed that two PU.1 motifs, which were located around +1100 bp downstream of the transcriptional start site of the HOTAIRM1 promoter, were responsible for the PU.1-dependent transactivation. The induction of HOTAIRM1 by ATRA was dependent on PU.1, and ectopic expression of PU.1 significantly up-regulated HOTAIRM1. Furthermore, low HOTAIRM1 expression was observed in APL cells, which was attributed to the reduced PU.1 expression rather than the repression by PML-RARα via the direct binding.
PU.1 directly activates the expression of HOTAIRM1 through binding to the regulatory region of HOTAIRM1 during granulocytic differentiation. The reduced PU.1 expression, rather than PML-RARα itself, results in the low expression of HOTAIRM1 in APL cells. Our findings enrich the knowledge on the regulation of lncRNAs and the underlying mechanisms of the abnormal expression of lncRNAs involved in APL.
Additional file 1: Figure S1. Arsenic trioxide had minimal effect on the expression levels of HOTAIRM1 and PU.1. Table S1: Primers for RT-qPCR. Table S2: Primers for ChIP-qPCR. (DOCX 35 kb)13045_2016_274_MOESM1_ESM.docx
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- PU.1 controls the expression of long noncoding RNA HOTAIRM1 during granulocytic differentiation
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