"Achieving transcriptional singularity.”

Title:
 "Achieving transcriptional singularity.” 

Abstract:
To detect volatile chemicals mammals committed ~4% of their gene-coding capacity in olfactory receptor (OR) genes. To perceive the identity of these chemicals, OR genes must follow the “one receptor per neuron” rule, whereby each olfactory sensory neuron expresses 1 out of 2800 OR alleles.  Transcriptional singularity is achieved by superimposed genetic and epigenetic mechanism that gradually reduce the complexity of OR transcription until only one allele remains transcriptionally active. First, a dorsoventral gradient of transcription factors NFIA, B, and X restricts OR choice to 50-200 OR identities. Then, highly specific interchromosomal genomic interactions enable the assembly of a few multi-enhancer hubs that activate transcription of 5-15 OR alleles with proper dorsoventral credentials. These multi-chromosomal enhancer hubs form by a tripartite protein complex (Lhx2/Ebf/Ldb1), which upon binding to OR enhancers undergoes “solid phase transitions” that explain how stable interchromosomal contacts are biochemically feasible. The nascent OR RNA produced in each of these hubs acts as long non-coding RNA that enhances its own transcription and silences OR transcription in competing hubs, orchestrating a “symmetry breaking” process that culminates in absolute transcriptional singularity. Finally, a signal elicited by OR protein translation in the ER stabilizes singular OR gene choice for the life of the neuron and transforms OR protein identity into axon guidance precision. 

About the MoGen Colloquium Series 2026:
The Colloquium series is paired with the first-year grad course (MMG 1003H), where students read a research paper by the speaker in a small group discussion, and participate in a Q&A with the speaker following the seminar.  This is a highly engaging session for the students and invited speaker, as the students raise interesting questions and directions for the speaker, and learn more about the research trajectory!

*Attached is the full colloquium speaker schedule and speaker bio-sketch.

Hope you will join us!

Josh