Chicken CCDC152 shares an NFYB-regulated bidirectional promoter with a growth hormone receptor antisense transcript and inhibits cells proliferation and migration

2017 
// Shudai Lin 1 , Wei Luo 1 , Mingya Jiang 1 , Wen Luo 1 , Bahareldin Ali Abdalla 1 , Qinghua Nie 1 , Li Zhang 2 and Xiquan Zhang 1 1 Guangdong Provincial Key Lab of Agro-Animal Genomics and Molecular Breeding and Key Lab of Chicken Genetics, Breeding and Reproduction, Ministry of Agriculture, College of Animal Science of South China Agricultural University, Guangzhou 510642, P.R. China 2 Agricultural College, Guangdong Ocean University, Zhanjiang 524088, P.R. China Correspondence to: Xiquan Zhang, email: xqzhang@scau.edu.cn Li Zhang, email: zhangli761101@163.com Keywords: bidirectional promoter, GHR antisense transcript, coiled-coil domain containing 152, NFYB, cell cycle Received: December 15, 2016      Accepted: September 04, 2017      Published: September 20, 2017 ABSTRACT The chicken coiled-coil domain-containing protein 152 ( CCDC152 ) recently has been identified as a novel one implicated in cell cycle regulation, cellular proliferation and migration by us. Here we demonstrate that CCDC152 is oriented in a head-to-head configuration with the antisense transcript of growth hormone receptor ( GHR ) gene. Through serial luciferase reporter assays, we firstly identified a minimal 102 bp intergenic region as a core bidirectional promoter to drive basal transcription in divergent orientations. And site mutation and transient transfected assays showed that nuclear transcription factor Y subunit beta (NFYB) could bind to the CCAAT box and directly transactivate this bidirectional promoter. SiRNA-mediated NFYB depletion could significantly down-regulate the expression of both GHR-AS-I6 and CCDC152 . Additionally, the expression of GHR-AS-I6 was significantly up-regulated after CCDC152 overexpression. Overexpression of CCDC152 remarkably reduced cell proliferation and migration through JAK2/STAT signaling pathway. Thus, the GHR-AS-I6–CCDC152 bidirectional transcription unit, as a novel direct target of NFYB, is possibly essential for the accelerated proliferation and motility of different cells.
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