Blimp1/PRDM1 functional roles in adult homeostasis. (360G-Wellcome-089157_Z_09_Z)

The zinc finger transcriptional repressor Blimp-1/PRDM1 plays key roles guiding development of multiple cell types, due to its ability to globally change gene expression patterns. New experiments demonstrate strong Blimp-1/PRDM1 expression in the intestinal crypts of the adult gut. Additionally we have discovered that a novel isoform with structurally diverse zinc finger domains encoded by alternatively spliced transcripts becomes localized to speckles in the nucleus, is selectively expressed by immature dendritic cells. Based on these results, this application outlines gene targeting experiments together with biochemical approaches, to investigate its activities. Conditional inactivation strategies, cell marking and lineage tracing experiments, aim to describe Blimp-1/PRDM1 functional contributions to dendritic cell maturation and adult gut homeostasis. The proposed experiments collectively should help us to understand how Blimp-1/PRDM1 acts in diverse cell types to select gene expres sion patterns, to instruct progenitors to become terminally differentiated or undergo renewal.