Abstract
OCT4 is a transcription factor known for its regulatory roles in stemness, tumorigenesis and stress response. Considering its versatile functions, expression of OCT4 is regulated at different levels. PSORS1C3, a long non-coding RNA overlapped with OCT4, has a putative association with immune mediated diseases; however, its exact functions remained to be elucidated. Here, we demonstrated that PSORS1C3 is regulated by glucocorticoids (GC), has two endogenously active promoters, promoter 0 and 1, and two sets of transcripts, short and long variants. According to our findings, PSORS1C3 promoters behaved differently during neural differentiation of NT2 cells and glucocorticoid receptor (GR) activation. In both processes the expression pattern of short variants differed from that of long variants and was similar to OCT4 expression. Furthermore, our data revealed that PSORS1C3’s promoter 0 could act as an enhancer for OCT4 in non-pluripotent cells, where its deletion caused a significant decrease in OCT4 expression. Meanwhile, during GR activation promoter 0 functioned as a negative regulator and alleviated transcription induction of OCT4 after GC treatment. Altogether, our work clarified the structure and regulation of PSORS1C3, explained its relation to immune-related disease through GR signaling and introduced it as a novel fine-tuner of OCT4 expression in non-pluripotent cells.
Highlights
OCT4, named POU5F1, is the main regulator of pluripotency in stem cells[1]
According to ENCODE CHIPseq data, PSORS1C3 promoter 0 could interact with 22 different transcription factors (TF, Fig. 1A)
Transcriptional regulation is one of the main mechanisms for cells to control the expression of different genes[16]
Summary
OCT4, named POU5F1, is the main regulator of pluripotency in stem cells[1] It has a part in tumorigenesis, cellular stress response, and is linked to various diseases from cancer to autoimmune disorders[2,3,4]. Long non-coding RNAs (lncRNAs) are non-protein coding transcripts with a size of more than 200 nucleotides They are capable of regulating gene expression with different mechanisms such as acting as guiding molecules, scaffold and RNA or protein decoy or distributer. Apart from their transcripts, the genomic elements residing in lncRNAs locus, like their promoters, could exert regulatory roles on their neighboring or even distant genes[9,10,11]. The exact molecular function of PSORS1C3 or its probable regulatory effect on OCT4 gene was not identified
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