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; OMA:SPI1 - orthologs
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 granulocyte monocyte right lung upper lobe of left lung spleen blood bone marrow cells appendix right coronary artery lymph node Top expressed in granulocyte tibiofemoral joint mesenteric lymph nodes stroma of bone marrow spleen blood medulla of thymus embryo lip ankle joint 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
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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 SWI/SNF,^[8] 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 .^[9]

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.^[10]

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,^[11]
• GATA2,^[12]
• IRF4,^[13][14] and
• NONO.^[15]