Meet the speaker
If you want to meet Dr. Boris Lenhard on Tuesday June 6th in Forskningsparken, please book a time slot using the jotform at https://eu.jotform.com/form/231443840945357.
Abstract
In a typical Metazoan genome, enhancers outnumber gene promoters by one or two orders of magnitude.Many genes that encode developmental regulators are influenced by numerous enhancers—sometimes in the hundreds—that may be positioned several megabases away from the target gene. Often, these enhancers are located within introns of neighbouring genes that do not react to their activity. Under such conditions, the task of accurately associating enhancers with their intended target genes becomes complex, and currently available methodologies fall short of providing optimal solutions.
Understanding the principles governing the specific interactions between enhancers and promoters, particularly across large genomic distances, is crucial for elucidating regulatory network architectures and interpreting genome-wide association studies accurately. Our analysis of promoter and enhancer activities, considering their chromatin contacts across a wide range of human or mouse tissues, reveals that most developmental genes exhibit a 1:many relationship with their distant enhancers, whereby numerous enhancers regulate a single gene, enclosed within the same topologically associating domain (TAD). Other genes within the TAD, generally displaying broad expression, are minimally responsive to the enhancer activity at the locus. This pattern supports the genomic regulatory block (GRB) model, effectively distinguishing the intended targets of long-range regulation from non-responsive "bystander" genes. Conversely, immune system-related gene loci demonstrate a robust many-to-many relationship, often encompassing all enhancers at their locus, suggesting the creation of transcription hubs for these genes. Different modes of promoter-enhancer interactions correlate closely with different classes of the promoters and underlying architectures.
Junior talk
TBD