Analysis of the Drosophila and Human DPR Elements Reveals a Distinct Human Variant Whose Specificity Can Be Enhanced by Machine Learning

The RNA polymerase II core promoter is the site of convergence of the signals that lead to the initiation of transcription. Here, we perform a comparative analysis of the downstream core promoter region (DPR) in Drosophila and humans by using machine learning. These studies revealed a distinct human-specific version of the DPR and led to the use of the machine learning models for the identification of synthetic extreme DPR motifs with specificity for human transcription factors relative to Drosophila factors, and vice versa. More generally, machine learning models could be analogously used to design synthetic promoter elements with customized functional properties. Overall design: HARPE and SVR analyses of the Drosophila downstream core promoter region (DPR). Its properties were compared to those of its human counterpart (Vo ngoc et al. 2020).