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 SOX9
Homo sapiens
 HIF1A
Homo sapiens
 Pax6
Mus musculus
 PAX6
Homo sapiens
 Snai2
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 PPARA
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Transcription Factor Encyclopedia  BETA
Comments (post)
Visitor (IP 71.60.57.204) on November 07, 2013 wrote:
 The overview text states that this factor is encoded by the gene Sfpi1. However, the approved HUGO Gene Nomenclature Committee (http://www.genenames.org) has designated "SPI1" as the approved symbol and "spleen focus forming virus (SFFV) proviral integration oncogene" as the approved gene name. 
Overview

The ETS transcription factor PU.1 (OF; PU.1; SFPI1; SPI-1; SPI-A; SPI) is encoded by the gene Sfpi1, which are located on human chr 11 and in the mouse on chr 2. PU.1 was first identified in mice by its erythroleukemia promoting activity as the result of spleen focus forming virus proviral integration into and subsequent activation of the spi-1 gene[1][2]. The ETS subfamily members, Ets, Elf, Erg, Tel, PEA, and other members are often transcriptional activators and expressed in many cell types. In contrast, PU.1 is predominantly expressed in various hematopoietic lineages and, interestingly, in the germinal compartment of embryonic testis, at least from E12.5 onward. Two PU.1 protein isoforms are produced from the spi-1 gene, a 271 aa and a 270 aa (~31 kDa) protein, which are able to bind as monomers via the C-terminal 84 aa ETS domain, a hallmark of ETS factors, to target genes containing the purine rich consensus sequence 5'-AAAG(A/C/G)GGAAG-3'. PU.1 activates transcription via its N-terminal glutamine-rich and acidic domains. The PU.1 ETS domain binds the 5'-GGAA-3' core sequence by a loop-helix-loop motif [3]. Since many myeloid genes are TATA-less, PU.1 functions as a basal transcription factor, and in many case, regulates gene expression in coordination with others transcription factors and cofactors. A large majority of myeloid growth and differentiation genes are regulated by PU.1, such as the macrophage colony-stimulating factor receptor (CSF R), granulocyte-CSF R, and granulocyte-macrophage-CSF R [4]. Moreover, PU.1 functions with many critical transcription factors needed for cellular functions, e.g., p53 [5], C/EBP alpha/beta/epsilon, gp91phox[6], GATA-1/-2[7], c-Jun, NONO, and MBP-P2. PU.1 is predominantly found in early hematopoietic progenitors, myeloid and early T cell lineage, monocytes/macrophages, granulocytes, and B lymphocytes. PU.1 may downregulate its target genes through epigenetic modification [8]. Loss of PU.1 expression and/or activity in hematopoietic cells results in blockage of myeloid differentiation at or just after the common myeloid progenitor stage. In the mouse, low levels of PU.1 result in abnormal differentiation and proliferation, eventually resulting in myeloid leukemia. In humans PU.1 expression is severely impaired in patients with chronic myeloid leukemia at diagnosis. However, the PU.1 suppression is abrogated after interferon-alpha or imatinib treatment. These effects are not found in patients with other myeloproliferative diseases such as polycythemia vera or essential thrombocythemia[9].

References
  1. Moreau-Gachelin F et al. Spi-1 is a putative oncogene in virally induced murine erythroleukaemias. Nature, 331(6153):277-80. (PMID 2827041)
  2. Klemsz MJ et al. The macrophage and B cell-specific transcription factor PU.1 is related to the ets oncogene. Cell, 61(1):113-24. (PMID 2180582)
  3. Pio F et al. New insights on DNA recognition by ets proteins from the crystal structure of the PU.1 ETS domain-DNA complex. J. Biol. Chem., 271(38):23329-37. (PMID 8798534)
  4. Tenen DG et al. Transcription factors, normal myeloid development, and leukemia. Blood, 90(2):489-519. (PMID 9226149)
  5. Tschan MP et al. PU.1 binding to the p53 family of tumor suppressors impairs their transcriptional activity. Oncogene, 27(24):3489-93. (PMID 18193090)
  1. Anderson KL et al. PU.1 is a lineage-specific regulator of tyrosine phosphatase CD45. J. Biol. Chem., 276(10):7637-42. (PMID 11114304)
  2. Zhang P et al. PU.1 inhibits GATA-1 function and erythroid differentiation by blocking GATA-1 DNA binding. Blood, 96(8):2641-8. (PMID 11023493)
  3. Suzuki M et al. Site-specific DNA methylation by a complex of PU.1 and Dnmt3a/b. Oncogene, 25(17):2477-88. (PMID 16331260)
  4. Albajar M et al. PU.1 expression is restored upon treatment of chronic myeloid leukemia patients. Cancer Lett., 270(2):328-36. (PMID 18635311)
Figures
FIGURE 1 PU.1 is necessary for hematopoietic differentiation.
PU.1 is required for the differentiation of common myeloid progenitors (CMP) and granulocyte/monocyte precursors (GMP ) to granulocyte, monocyte and dendritic cells (DC). PU.1-deficient myeloid progenitors are not able to differentiate and are halted in differentiation after the CMP stage.
This figure was created by the authors of this article. The authors of this article have provided the assurance that this figure constitutes their original work.