Expression of SOX-11 and SOX-4, and activity of LINE-1 retrotransposons during neuronal differentiation

CINTIA GATTI; ANDRES J ORQUEDA

Congreso; JOINT MEETING OF BIOSCIENCE SOCIETIES; 2017

Sox-4 and Sox-11 are single-exon genes members of the Sox-C transcription factors family. Evidence has shown critical roles for both genes in multiple developmental processes, particularly during the central nervous system development, probably with redundant functions. On the other hand, Long Interspersed Nuclear Elements-1 (LINE-1) retrotransposons are repetitive elements that encode an RNA binding protein and an endonuclease with reverse transcriptase activity, under the control of a promoter in the 5´UTR; both proteins modulate LINE-1 mobilization. Human LINE-1 insertions occur mainly during early embryonic development, although somatic retrotransposition occurs also in neuronal progenitor cells. Despite a Sox-11 binding site has been described in the LINE-1 5´UTR, it has not been addressed before whether Sox-C members control LINE-1 activity in the neuronal lineage. With that aim, we decided to evaluate the expression of Sox-4 and -11 in LINE-1 retrotransposition conditions of neuronal differentiation of neuroblastoma cells cultured with retinoic acid (RA). First, we observed that LINE-1 promoter activity increases in human SH-SY5Y and mouse Neuro-2A cells treated with RA, as shown by wild type 5´UTR-driven luciferase activity, compared to basal conditions. Next, we studied Sox-4 and -11 RNA levels by RT-qPCR, and found that expression of both genes increases in RA-treated SH-SY5Y cells. Finally, immunohistochemistry assays showed a higher abundance of Sox-11 protein in nuclei of both cell types challenged with RA, compared to control non treated cells. Thus, our results suggest that both Sox-4 and -11 expression and LINE-1 activity are increased in neuronal differentiation conditions; also, that RA probably induces Sox-11 translocation to nucleus. Because the knock-down of these transcription factors has not been done yet, it remains to be determined whether one or both proteins indeed control LINE-1 activity during neuronal differentiation.