31 March 2023
Arnaud Krebs
EMBL, Heidelberg
Germany
Transcription Factors (TFs) are the primary regulators of gene expression. Activation of a gene typically results from the cooperative action of multiple TFs that open chromatin at cis-regulatory elements, and subsequently recruit the general transcription machinery. In the last decades, genomics has enabled the generation of a near-complete annotation of the cis-regulatory elements and the TFs binding them across cell types. Despite this, the precise mechanisms used by TFs to activate transcription remains largely elusive. Current models are mostly built on bulk genomics data, where genome-occupancy signals are averaged across millions of cells, a level of resolution that is insufficient to understand collective TF function. I will discuss how the emergence of single-cell and single-molecule genomics is overcoming some of these limitations by providing with snapshots of TF occupancy and chromatin states across entire cell populations. I will put in perspective the new type of information gained by these assays and propose how it may contribute to the quantitative models of TF function.