DNA actively contributes to gene expression of paired transcription factors

Abstract

DNA, by interacting with transcriptional regulators, determines gene expression, yet it is not known whether the DNA sequence itself actively contributes to gene expression. Here we show that changing the nucleotide sequence interposed between CRX and NRL binding sites (BS) of theRHODOPSIN(RHO) promoter led to uncorrelated gene expression variation. Mutual exchange of human and mouse homolog CRX-NRL-linking sequences, although divergent, conferred similar and species-specific gene expression levels. Interfering these DNA features with orthogonal proteins enables differential gene expression depending on the orientation linker sequence relative to the two BS. The results imply an active role of DNA itself in determining RHO expression levels.