PU1

PU.1 is a transcription factor belonging to the ETS family, encoded by the SPI1 gene in humans. It plays a central role in hematopoiesis, particularly in the development of myeloid lineages and B lymphocytes. PU.1 functions by binding to regulatory DNA sequences via its ETS domain and coordinating with other transcription factors to activate or repress target genes involved in differentiation, proliferation, and immune responses.

The activity and expression level of PU.1 in progenitor cells influence cell fate decisions. High PU.1 activity promotes macrophage and dendritic cell programs, while lower levels favor neutrophil differentiation. In B cells, PU.1 is required for early lineage specification and receptor assembly, but excessive or prolonged PU.1 activity can impede progression at later stages. The effects of PU.1 are modulated by interactions with other factors such as GATA-1 and C/EBPα, reflecting a balance that guides lineage outcomes.

Regulation of PU.1 occurs at multiple levels, including transcriptional control, post-translational modifications, and signaling pathways. Cytokines and signaling cascades, including GM-CSF, IL-7, and CSF1 pathways, influence PU.1 expression and activity. Epigenetic context and chromatin accessibility also shape PU.1 binding to enhancers and promoters across the genome.

Clinical relevance of PU.1 lies in its role as a gatekeeper of hematopoietic differentiation. Altered PU.1 expression or function has been associated with hematological disorders, including myeloid and lymphoid malignancies, where disrupted lineage commitment contributes to disease development. Because of its pivotal role, PU.1 remains a focus of research into normal hematopoiesis and leukemogenesis.

See also: SPI1, ETS transcription factors, hematopoiesis.