SPI1

Transcription factor PU.1 is a protein that in humans is encoded by the SPI1 gene.^[5]

SPI1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1PUE
Identifiers
Aliases	SPI1, OF, PU.1, SFPI1, SPI-1, SPI-A, Spi-1 proto-oncogene, AGM10
External IDs	OMIM: 165170 MGI: 98282 HomoloGene: 2346 GeneCards: SPI1
Gene location (Human) Chr. Chromosome 11 (human)^[1] Band 11p11.2 Start 47,354,860 bp^[1] End 47,378,547 bp^[1]
Gene location (Mouse) Chr. Chromosome 2 (mouse)^[2] Band 2 E1|2 50.44 cM Start 90,912,735 bp^[2] End 90,946,101 bp^[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in monocyte right lung upper lobe of left lung spleen blood bone marrow cells appendix right coronary artery lymph node gallbladder Top expressed in spleen blood lip ankle joint subcutaneous adipose tissue body of femur right lung lobe calvaria white adipose tissue ankle More reference expression data BioGPS More reference expression data
Gene ontology Molecular function DNA binding sequence-specific DNA binding DNA-binding transcription activator activity, RNA polymerase II-specific RNA polymerase II cis-regulatory region sequence-specific DNA binding transcription factor activity, RNA polymerase II core promoter proximal region sequence-specific binding DNA-binding transcription repressor activity, RNA polymerase II-specific protein binding RNA binding transcription factor activity, RNA polymerase II distal enhancer sequence-specific binding DNA-binding transcription factor activity NFAT protein binding DNA-binding transcription factor activity, RNA polymerase II-specific transcription factor binding Cellular component nucleus nucleoplasm transcription regulator complex Biological process myeloid leukocyte differentiation regulation of transcription, DNA-templated cellular response to ethanol somatic stem cell population maintenance lymphocyte differentiation regulation of erythrocyte differentiation myeloid dendritic cell differentiation negative regulation of transcription by RNA polymerase II negative regulation of MHC class II biosynthetic process lymphoid progenitor cell differentiation transcription, DNA-templated macrophage differentiation anatomical structure regression negative regulation of histone H4 acetylation negative regulation of gene expression, epigenetic vasculature development granulocyte differentiation apoptotic process involved in blood vessel morphogenesis histone H3 acetylation erythrocyte differentiation hypermethylation of CpG island positive regulation of pri-miRNA transcription by RNA polymerase II positive regulation of transcription by RNA polymerase II negative regulation of transcription, DNA-templated positive regulation of transcription, DNA-templated regulation of transcription by RNA polymerase II pri-miRNA transcription by RNA polymerase II cell differentiation interleukin-6-mediated signaling pathway Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 6688 20375 Ensembl ENSG00000066336 ENSMUSG00000002111 UniProt P17947 P17433 RefSeq (mRNA) NM_001080547 NM_003120 NM_011355 NM_001378898 NM_001378899 RefSeq (protein) NP_001074016 NP_003111 NP_035485 NP_001365827 NP_001365828 Location (UCSC) Chr 11: 47.35 – 47.38 Mb Chr 2: 90.91 – 90.95 Mb PubMed search ^[3] ^[4]
Wikidata
View/Edit Human View/Edit Mouse

Function

This gene encodes an ETS-domain transcription factor that activates gene expression during myeloid and B-lymphoid cell development.^[6] The nuclear protein binds to a purine-rich sequence known as the PU-box found on enhancers of target genes, and regulates their expression in coordination with other transcription factors and cofactors. The protein can also regulate alternative splicing of target genes. Multiple transcript variants encoding different isoforms have been found for this gene.^[7]

The PU.1 transcription factor is essential for hematopoiesis and cell fate decisions. PU.1 can physically interact with a variety of regulatory factors like TFIID, GATA-2, GATA-1 and c-Jun. The protein-protein interactions between these factors can regulate PU.1-dependent cell fate decisions. PU.1 can modulate the expression of 3000 genes in hematopoietic cells including cytokines. It is expressed in monocytes, granulocytes, B and NK cells but is absent in T cells, reticulocytes and megakaryocytes. Its transcription is regulated by various mechanisms .^[8]

PU.1 is an essential regulator of the pro-fibrotic system. In fibrotic conditions, PU.1 expression is perturbed in fibrotic diseases, resulting in upregulation of fibrosis-associated genes sets in fibroblasts. Disruption of PU.1 in fibrotic fibroblasts leads to them returning into their resting state from pro-fibrotic fibroblasts. PU.1 is seen to be highly expressed in extracellular matrix producing-fibrotic fibroblasts while it is downregulated in inflammatory/ ECM degrading and resting fibroblasts. The majority of the cells expressing PU.1 in fibrotic conditions remain to be fibroblasts with a few infiltrating lymphocytes. PU.1 induces the polarization of resting and inflammatory fibroblasts into fibrotic fibroblasts.^[9]

Structure

The ETS domain is the DNA-binding module of PU.1 and other ETS-family transcription factors.

Interactions

SPI1 has been shown to interact with:

• FUS,^[10]
• GATA2,^[11]
• IRF4,^[12][13] and
• NONO.^[14]

References

1. GRCh38: Ensembl release 89: ENSG00000066336 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000002111 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Ray D, Culine S, Tavitain A, Moreau-Gachelin F (May 1990). "The human homologue of the putative proto-oncogene Spi-1: characterization and expression in tumors". Oncogene. 5 (5): 663–668. PMID 1693183.
6. Oikawa T, Yamada T, Kihara-Negishi F, Yamamoto H, Kondoh N, Hitomi Y, Hashimoto Y (July 1999). "The role of Ets family transcription factor PU.1 in hematopoietic cell differentiation, proliferation and apoptosis". Cell Death and Differentiation. 6 (7): 599–608. doi:10.1038/sj.cdd.4400534. PMID 10453070.
7. "Entrez Gene: SPI1 spleen focus forming virus (SFFV) proviral integration oncogene spi1".
8. Burda P, Laslo P, Stopka T (July 2010). "The role of PU.1 and GATA-1 transcription factors during normal and leukemogenic hematopoiesis". Leukemia. 24 (7): 1249–1257. doi:10.1038/leu.2010.104. PMID 20520638. S2CID 1941766.
9. Wohlfahrt T, Rauber S, Uebe S, Luber M, Soare A, Ekici A, et al. (February 2019). "PU.1 controls fibroblast polarization and tissue fibrosis". Nature. 566 (7744): 344–349. doi:10.1038/s41586-019-0896-x. PMC 6526281. PMID 30700907.
10. Hallier M, Lerga A, Barnache S, Tavitian A, Moreau-Gachelin F (February 1998). "The transcription factor Spi-1/PU.1 interacts with the potential splicing factor TLS". The Journal of Biological Chemistry. 273 (9): 4838–4842. doi:10.1074/jbc.273.9.4838. PMID 9478924.
11. Zhang P, Behre G, Pan J, Iwama A, Wara-Aswapati N, Radomska HS, et al. (July 1999). "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. Bibcode:1999PNAS...96.8705Z. doi:10.1073/pnas.96.15.8705. PMC 17580. PMID 10411939.
12. Brass AL, Zhu AQ, Singh H (February 1999). "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. PMC 1171190. PMID 10022840.
13. Escalante CR, Shen L, Escalante MC, Brass AL, Edwards TA, Singh H, Aggarwal AK (July 2002). "Crystallization and characterization of PU.1/IRF-4/DNA ternary complex". Journal of Structural Biology. 139 (1): 55–59. doi:10.1016/s1047-8477(02)00514-2. PMID 12372320.
14. Hallier M, Tavitian A, Moreau-Gachelin F (May 1996). "The transcription factor Spi-1/PU.1 binds RNA and interferes with the RNA-binding protein p54nrb". The Journal of Biological Chemistry. 271 (19): 11177–11181. doi:10.1074/jbc.271.19.11177. PMID 8626664.

Further reading

• Klemsz MJ, McKercher SR, Celada A, Van Beveren C, Maki RA (April 1990). "The macrophage and B cell-specific transcription factor PU.1 is related to the ets oncogene". Cell. 61 (1): 113–124. doi:10.1016/0092-8674(90)90219-5. PMID 2180582. S2CID 27819155.
• Nguyen VC, Ray D, Gross MS, de Tand MF, Frézal J, Moreau-Gachelin F (May 1990). "Localization of the human oncogene SPI1 on chromosome 11, region p11.22". Human Genetics. 84 (6): 542–546. doi:10.1007/bf00210807. PMID 2338340. S2CID 22337200.
• Chen H, Ray-Gallet D, Zhang P, Hetherington CJ, Gonzalez DA, Zhang DE, et al. (October 1995). "PU.1 (Spi-1) autoregulates its expression in myeloid cells". Oncogene. 11 (8): 1549–1560. PMID 7478579.
• Nagulapalli S, Pongubala JM, Atchison ML (November 1995). "Multiple proteins physically interact with PU.1. Transcriptional synergy with NF-IL6 beta (C/EBP delta, CRP3)". Journal of Immunology. 155 (9): 4330–4338. doi:10.4049/jimmunol.155.9.4330. PMID 7594592.
• Pongubala JM, Atchison ML (April 1995). "Activating transcription factor 1 and cyclic AMP response element modulator can modulate the activity of the immunoglobulin kappa 3' enhancer". The Journal of Biological Chemistry. 270 (17): 10304–10313. doi:10.1074/jbc.270.17.10304. PMID 7730336.
• Hromas R, Orazi A, Neiman RS, Maki R, Van Beveran C, Moore J, Klemsz M (November 1993). "Hematopoietic lineage- and stage-restricted expression of the ETS oncogene family member PU.1". Blood. 82 (10): 2998–3004. doi:10.1182/blood.V82.10.2998.2998. PMID 8219191.
• Hagemeier C, Bannister AJ, Cook A, Kouzarides T (February 1993). "The activation domain of transcription factor PU.1 binds the retinoblastoma (RB) protein and the transcription factor TFIID in vitro: RB shows sequence similarity to TFIID and TFIIB". Proceedings of the National Academy of Sciences of the United States of America. 90 (4): 1580–1584. Bibcode:1993PNAS...90.1580H. doi:10.1073/pnas.90.4.1580. PMC 45918. PMID 8434021.
• Hallier M, Tavitian A, Moreau-Gachelin F (May 1996). "The transcription factor Spi-1/PU.1 binds RNA and interferes with the RNA-binding protein p54nrb". The Journal of Biological Chemistry. 271 (19): 11177–11181. doi:10.1074/jbc.271.19.11177. PMID 8626664.
• Bassuk AG, Anandappa RT, Leiden JM (May 1997). "Physical interactions between Ets and NF-kappaB/NFAT proteins play an important role in their cooperative activation of the human immunodeficiency virus enhancer in T cells". Journal of Virology. 71 (5): 3563–3573. doi:10.1128/JVI.71.5.3563-3573.1997. PMC 191503. PMID 9094628.
• Li SL, Valente AJ, Zhao SJ, Clark RA (July 1997). "PU.1 is essential for p47(phox) promoter activity in myeloid cells". The Journal of Biological Chemistry. 272 (28): 17802–17809. doi:10.1074/jbc.272.28.17802. PMID 9211934.
• Tsukada J, Misago M, Serino Y, Ogawa R, Murakami S, Nakanishi M, et al. (October 1997). "Human T-cell leukemia virus type I Tax transactivates the promoter of human prointerleukin-1beta gene through association with two transcription factors, nuclear factor-interleukin-6 and Spi-1". Blood. 90 (8): 3142–3153. doi:10.1182/blood.V90.8.3142. PMID 9376596.
• Hallier M, Lerga A, Barnache S, Tavitian A, Moreau-Gachelin F (February 1998). "The transcription factor Spi-1/PU.1 interacts with the potential splicing factor TLS". The Journal of Biological Chemistry. 273 (9): 4838–4842. doi:10.1074/jbc.273.9.4838. PMID 9478924.
• Suzuki S, Kumatori A, Haagen IA, Fujii Y, Sadat MA, Jun HL, et al. (May 1998). "PU.1 as an essential activator for the expression of gp91(phox) gene in human peripheral neutrophils, monocytes, and B lymphocytes". Proceedings of the National Academy of Sciences of the United States of America. 95 (11): 6085–6090. Bibcode:1998PNAS...95.6085S. doi:10.1073/pnas.95.11.6085. PMC 27589. PMID 9600921.
• Carrère S, Verger A, Flourens A, Stehelin D, Duterque-Coquillaud M (June 1998). "Erg proteins, transcription factors of the Ets family, form homo, heterodimers and ternary complexes via two distinct domains". Oncogene. 16 (25): 3261–3268. doi:10.1038/sj.onc.1201868. PMID 9681824. S2CID 26807714.
• Sato M, Morii E, Takebayashi-Suzuki K, Yasui N, Ochi T, Kitamura Y, Nomura S (January 1999). "Microphthalmia-associated transcription factor interacts with PU.1 and c-Fos: determination of their subcellular localization". Biochemical and Biophysical Research Communications. 254 (2): 384–387. doi:10.1006/bbrc.1998.9918. PMID 9918847.
• Brass AL, Zhu AQ, Singh H (February 1999). "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. PMC 1171190. PMID 10022840.
• Yamamoto H, Kihara-Negishi F, Yamada T, Hashimoto Y, Oikawa T (February 1999). "Physical and functional interactions between the transcription factor PU.1 and the coactivator CBP". Oncogene. 18 (7): 1495–1501. doi:10.1038/sj.onc.1202427. PMID 10050886.
• Rao S, Matsumura A, Yoon J, Simon MC (April 1999). "SPI-B activates transcription via a unique proline, serine, and threonine domain and exhibits DNA binding affinity differences from PU.1". The Journal of Biological Chemistry. 274 (16): 11115–11124. doi:10.1074/jbc.274.16.11115. PMID 10196196.
• Mao S, Frank RC, Zhang J, Miyazaki Y, Nimer SD (May 1999). "Functional and physical interactions between AML1 proteins and an ETS protein, MEF: implications for the pathogenesis of t(8;21)-positive leukemias". Molecular and Cellular Biology. 19 (5): 3635–3644. doi:10.1128/mcb.19.5.3635. PMC 84165. PMID 10207087.

External links

• FactorBook PU.1