WEHI PhD Completion Seminar hosted by Associate Professor Rhys Allan

Wenxin (Wendy) Jia
PhD Student – Allan Laboratory, Immunity division, WEHI

Dissecting the role of PU.1 in the 3D genome landscape of granulopoiesis

Davis Auditorium

Join via TEAMS

Including Q&A session

During haematopoiesis, master transcription factors must simultaneously activate lineage specific gene networks and repress non-lineage circuitry.  While the mechanisms of direct gene activation by master regulators are well characterised, how they sustainably restrict alternative lineage differentiation remains incompletely understood. Using granulopoiesis as a model, I investigated the role of the pioneer myeloid factor PU.1 in directing terminal differentiation.

To understand the molecular underpinnings of this process, during my PhD, I upskilled in bioinformatics and combined it with my wet lab experience to perform multi-omics profiling (transcriptomics, ChIP-seq, CUT&RUN and Hi-C) of the conditional deletion of PU.1 in vivo in granulocytes. My findings show that during normal granulopoiesis, PU.1 and the shared multi-lineage factor Runx1 co-associate to drive the establishment of 3D genome architecture around myeloid loci. However, in PU.1-deficient granulocytes this architecture weakens, Runx1 redistributes to highly accessible promoters, and cells undergo a profound identity crisis—maintaining expression of progenitor genes alongside the ectopic activation of early T cell and megakaryocyte development programs.  

Thus, my work propose that 3D spatial sequestration is a fundamental driver of cellular identity and that haematopoietic fate is determined not merely by the induction of lineage-specific genes, but by the architectural confinement of shared developmental machinery.

All welcome!