title: Downregulation of long noncoding RNA HOTAIRM1 promotes monocyte/dendritic cell differentiation through competitively binding to endogenous miR-3960.
abstract: Myeloid differentiation is controlled by a multilayered regulatory circuitry consisting of various elements, including histone modifications, transcription factors, and posttranscriptional regulators such as miRNAs, long noncoding RNAs, and circular RNAs. However, the molecular mechanism underlying this biological process remains unclear. In this study, through epigenetic profiling analysis using chromatin immunoprecipitation (ChIP) followed by sequencing (ChIP-seq), we identified an lncRNA, HOTAIRM1, with a critical role in myeloid development. Further ChIP-chip analysis showed obvious H3K4me3 and H3K27me3 histone modification peak changes in the promoter region of HOTAIRM1 during the process of monocyte to dendritic cell (DC) differentiation. In line with this observation, HOTAIRM1 RNA expression was downregulated when monocytes differentiated into DCs. Moreover, we found that HOTAIRM1 RNA was regulated by epigenetic factors such asRBBP4andRBBP7. Mechanistically, we found that the silencing of HOTAIRM1 caused changes in the expression of several monocyte differentiation markers such as CD14 and B7H2. In addition, based on the "competing endogenous RNA" hypothesis, we discovered miR-3960 targeting both HOTAIRM1 and the DC differentiation repression gene,HOXA1, by most possibly constructing a potential competing endogenous RNA network. Increased miR-3960 expression could downregulate both of these two long RNAs and finally lead peripheral blood cells to differentiate into DCs. In summary, our study demonstrates that HOTAIRM1 competitively binds to miR-3960 and finally regulates the process of hematopoiesis, which reveals a novel regulatory mechanism of lncRNA function.
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, People's Republic of China.
authors.forename: Jiaxuan
authors.initials: J
authors.lastname: Xin
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, People's Republic of China.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, People's Republic of China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Feng
authors.affiliation: Faculty of Medicine, University of Southampton, Southampton, UK.
authors.forename: Liyang
authors.initials: L
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, People's Republic of China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, People's Republic of China; Key Laboratory of Bioactive Materials, Ministry of Education; Department of Immunology, Nankai University School of Medicine, Nankai University, Tianjin, People's Republic of China.
authors.forename: Rongcun
authors.initials: R
authors.lastname: Yang
keywords: HOTAIRM1; lncRNA; miR-3960; myeloid cells; myeloid differentiation