zinc finger protein Gfi-1b (growth factor independent protein 1B, potential regulator of CDKN1A translocated in CML, GFI1B)

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Function

proto-oncogenic transcriptional regulator necessary for development & differentiation of erythroid & megakaryocytic lineages.
transcriptional repressor or activator depending on both promoter & cell type context
represses promoter activity of SOCS1 & SOCS3 & thus, may regulate cytokine signaling pathways
cooperates with GATA1 to repress target gene transcription, including apoptosis regulator BCL2L1
GFI1B silencing in leukemic cell lines markedly increase apoptosis
inhibits down-regulation of MYC & MYB as well as the cyclin-dependent kinase inhibitor CDKN1A/P21WAF1 in IL6-treated myelomonocytic cells
represses expression of GATA3 in T-cell lymphomas & inhibits GATA1-mediated transcription; as GATA1 also mediates erythroid GFI1B transcription, both GATA1 & GFI1B participate in a feedback regulatory pathway controlling the expression of GFI1B gene in erythroid cells
suppresses GATA1-mediated stimulation of GFI1B promoter through protein interaction
binds to gamma-satellite DNA & to its own promoter, auto-repressing its own expression
alters histone methylation by recruiting histone methyltransferase to target genes promoters
plays a role in heterochromatin formation
forms a complex with GATA1
interacts with histone methyltransferases EHMT2 & SUV39H1

zinc finger domains are essential for erythroid expansion & acts as an activation domain whereas non finger domain serves as repression domain (putative)
contains 6 C2H2-type zinc fingers

expressed in bone marrow & fetal liver
also detectable in fetal spleen, fetal thymus, & testes
detected in hematopoietic stem cells, erythroblasts, & megakaryocytes
induced by GATA1 which binds to GFI1B promoter in cooperation with the transcription factor NFYA.

overexpressed in bone marrow of patients with erythroleukemia & megakaryocytic leukemia as well as in their corresponding leukemic cell lines
markedly repressed in severe aplastic anemia
target gene of transcription factor E2-alpha/TCF3 that promotes growth arrest & apoptosis in lymphomas