Gfi1-cells and circuits: unraveling transcriptional networks of development and disease.
OBJECTIVE
The review will integrate current knowledge of transcriptional circuits whose dysregulation leads to autoimmunity, neutropenia and leukemia.


RESULTS
Growth factor independent-1 (Gfi1) is a transcriptional repressor with essential roles in controlling hematopoietic stem cell biology, myeloid and lymphoid differentiation and lymphocyte effector functions. Recent work has suggested that Gfi1 competes or collaborates with other transcription factors to modulate transcription programs and lineage decisions.


CONCLUSIONS
Gfi1 is central to several transcriptional circuits whose dysregulation leads to abnormal or malignant hematopoiesis. These functional relationships are conserved from Drosophila development. Such conserved pathways represent central oncogenic or 'gatekeeper' pathways that are pivotal to understanding the process of cellular transformation, and illustrate key targets for clinical intervention.
Phelan
James D
JD
Immunobiology Graduate Program, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA.
Shroyer
Noah F
NF
Cook
Tiffany
T
Gebelein
Brian
B
Grimes
H Leighton
HL
D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D053263:Gene Regulatory Networks; D006410:Hematopoiesis / Q000235:genetics / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D007938:Leukemia / Q000235:genetics / Q000503:physiopathology; D009503:Neutropenia / Q000235:genetics / Q000503:physiopathology; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*
D004268:DNA-Binding Proteins; C498275:GFI1 protein, human; D014157:Transcription Factors