Studying transcription factor function in the genome at molecular resolution

About 7% of the human genome encodes cis-regulatory elements (CREs) that function as regulatory switches to modulate the expression of genes. These short genetic sequences control the complex transcriptional changes necessary for organismal development. A topical challenge in the field is to understand how transcription factors (TFs) read and translate this information into gene expression patterns. Here, I review how the development of single-molecule footprinting (SMF) that resolves the genome occupancy of TFs on individual DNA molecules resolution contributes to our ability to establish how the regula-tory genetic information is interpreted at the mechanistic level. I further discuss how future developments in the nascent field of single-molecule genomics (SMG) could impact our understanding of gene regulation mechanisms.

Automated summary

About 7% of the human genome encodes cis-regulatory elements (CREs) that act as switches to regulate gene expression during organismal development. The challenge is to understand how transcription factors (TFs) interpret genetic information to influence gene expression patterns. The development of single-molecule footprinting (SMF) has aided in establishing the mechanistic interpretation of regulatory genetic information, and further advancements in single-molecule genomics (SMG) may impact our understanding of gene regulation mechanisms.