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SPI1 gene

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In humans the SPI1 gene is located on chromosome 11, specifically on the p arm of the chromosome [1] . The gene codes for the transcription factor PU.1. The transcript for PU.1 is 1333 nucleotides long and contains 5 exons. The PU.1 protein has 264 amino acids, with the DNA binding domain located in the carboxyl terminal of the protein. The Spi-1 gene is active in myeloid progenitor cells as well as lymphoid progenitor cells to initiate differentiation of the progenitor cells to mature immune system cells [2]. Some diseases associated with the SPI1 gene are Inflammatory Diarrhea and Interdigitating Dendritic Cell Sarcoma.

SPI1 has been shown to interact with:

PU.1 protein function

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The PU.1 protein is an ETS family transcription factor that is expressed in hematopoietic tissues, which are areas where new blood cells form [8]. The ETS domain of the PU.1 protein exhibits a winged helix-turn-helix motif with a loop-helix-loop architecture, and interacts with a 10-base-pair region on duplex DNA [8]. The PU.1 protein has been found to be needed for proper hematopoietic stem cell function and development [2]. Hematopoietic stem cell express PU.1, and its expression is needed for maintenance of the hematopoietic stem cell pool that is kept in the bone marrow [2].

Macrophages have the highest levels of PU.1 protein[9]. The PU.1 protein within macrophages control the expression of genes involved in macrophage differentiation and function[9]. The activation of the PU.1 protein allows for myeloid progenitor cells to differentiate and give rise to mature macrophages[9].

Previous research on the PU. 1 protein has found that it can act as an oncogene. To research this function of PU.1 proteins, the gene that encodes for this PU. 1 protein was mutated through gene targeting. When the gene was mutated, it was no longer functional. This lead to the indefinite proliferation of myeloid and lymphoid progenitor cells. Due to this the myeloid and lymphoid progenitor cells did not differentiate into mature immune system cells [9]. It was seen that mice without the PU.1 protein died after birth, as they were lacking both the myeloid and lymphoid lineage cells, thus showing lacking the PU. 1 protein is lethal [9].

Acute Myeloid Leukemia (AML)

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Acute myeloid leukemia (AML) is a form of blood cancer characterized by no differentiation of white blood cells. The PU.1 transcription factor is known to play a role in AML when mutated. When the gene is mutated is causes a decrease in differentiation of myeloid progenitor cells to white blood cells. Even only a slight reduction in PU.1 levels is enough to cause the AML phenotype.

Reference List

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  1. ^ "SPI1 Spi-1 proto-oncogene [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2016-11-20.
  2. ^ a b c Fisher, Robert C.; Scott, Edward W. (1998-01-01). "Role of PU.1 in Hematopoiesis". STEM CELLS. 16 (1): 25–37. doi:10.1002/stem.160025. ISSN 1549-4918.
  3. ^ Hallier, Marc; Lerga, Ana; Barnache, Stéphane; Tavitian, Armand; Moreau-Gachelin, Françoise (1998-02-27). "The Transcription Factor Spi-1/PU.1 Interacts with the Potential Splicing Factor TLS". Journal of Biological Chemistry. 273 (9): 4838–4842. doi:10.1074/jbc.273.9.4838. ISSN 0021-9258. PMID 9478924.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  4. ^ Zhang, P.; Behre, G.; Pan, J.; Iwama, A.; Wara-Aswapati, N.; Radomska, H. S.; Auron, P. E.; Tenen, D. G.; Sun, Z. (1999-07-20). "Negative cross-talk between hematopoietic regulators: GATA proteins repress PU.1". Proceedings of the National Academy of Sciences of the United States of America. 96 (15): 8705–8710. ISSN 0027-8424. PMC 17580. PMID 10411939.
  5. ^ Brass, A L; Zhu, A Q; Singh, H (1999-02-15). "Assembly requirements of PU.1-Pip (IRF-4) activator complexes: inhibiting function in vivo using fused dimers". The EMBO Journal. 18 (4): 977–991. doi:10.1093/emboj/18.4.977. ISSN 0261-4189. PMC 1171190. PMID 10022840.
  6. ^ Escalante, Carlos R.; Shen, Leyi; Escalante, Mary C.; Brass, Abraham L.; Edwards, Thomas A.; Singh, Harinder; Aggarwal, Aneel K. (2002-07-01). "Crystallization and characterization of PU.1/IRF-4/DNA ternary complex". Journal of Structural Biology. 139 (1): 55–59. ISSN 1047-8477. PMID 12372320.
  7. ^ Ridinger-Saison, M.; Evanno, E.; Gallais, I.; Rimmelé, P.; Selimoglu-Buet, D.; Sapharikas, E.; Moreau-Gachelin, F.; Guillouf, C. (2013-09-01). "Epigenetic silencing of Bim transcription by Spi-1/PU.1 promotes apoptosis resistance in leukaemia". Cell Death & Differentiation. 20 (9): 1268–1278. doi:10.1038/cdd.2013.88. ISSN 1350-9047. PMC 3741512. PMID 23852375.
  8. ^ a b Kastner, Philippe; Chan, Susan (2008-01-01). "PU.1: A crucial and versatile player in hematopoiesis and leukemia". The International Journal of Biochemistry & Cell Biology. 40 (1): 22–27. doi:10.1016/j.biocel.2007.01.026.
  9. ^ a b c d e Will, Britta; Vogler, Thomas O.; Narayanagari, Swathi; Bartholdy, Boris; Todorova, Tihomira I.; da Silva Ferreira, Mariana; Chen, Jiahao; Yu, Yiting; Mayer, Jillian (2015-10-01). "Minimal PU.1 reduction induces a preleukemic state and promotes development of acute myeloid leukemia". Nature Medicine. 21 (10): 1172–1181. doi:10.1038/nm.3936. ISSN 1078-8956.
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