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

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-tohead 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 GHRAS- I6-CCDC152 bidirectional transcription unit, as a novel direct target of NFYB, is possibly essential for the accelerated proliferation and motility of different cells.