Deciphering Transcriptome: Transcription Factors as Master Mind Behind Gene Expression

Abstract

Transcription Factors (TFs) are key players in orchestrating diversified transcriptomes across cell types. Known to function in co-operative pairs, TFs are dynamic and hard to be experimentally captured in motion. With an innovated scRNA-Seq technique, MALBAC-DT, the steady-state measurements were dissected deeper into the dynamic fluctuations. Provided with precise and accurate expression correlations, co-activated gene pairs were revealed to be expressed in the same cell at the same time, in contrast to the traditional terminology 'co-expression', which refers to the similar expression patterns across different cell populations. Further, in combination with motif analysis on open chromatin, we inferred the co-localized and co-activated combinatorial TF pairs (TF3C), which shed light onto the co-operative regulation of TFs on the target genes. Differential across cell types yet highly preserved within co-regulated gene clusters, TF3C led us to propose a transcription regulation scheme: gene looping of the target gene's promoter, enhancer, and TTS, assisted by the shared TF3Cs. Finally, we present a TF combinatorial regulation map that is unique to each cell-type, capturing the essence of the dynamic fluctuations otherwise convoluted in each cell population.