SPI1

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Protein-coding gene in the species Homo sapiens

title: "SPI1" type: doc version: 1 created: 2026-02-28 author: "Wikipedia contributors" status: active scope: public tags: ["transcription-factors"] description: "Protein-coding gene in the species Homo sapiens" topic_path: "arts/film" source: "https://en.wikipedia.org/wiki/SPI1" license: "CC BY-SA 4.0" wikipedia_page_id: 0 wikipedia_revision_id: 0

::summary Protein-coding gene in the species Homo sapiens ::

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

Function

This gene encodes an ETS-domain transcription factor that activates gene expression during myeloid and B-lymphoid cell development. 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.

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, 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 .

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

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:

References

References

  1. (May 1990). "The human homologue of the putative proto-oncogene Spi-1: characterization and expression in tumors". Oncogene.
  2. (July 1999). "The role of Ets family transcription factor PU.1 in hematopoietic cell differentiation, proliferation and apoptosis". Cell Death and Differentiation.
  3. "Entrez Gene: SPI1 spleen focus forming virus (SFFV) proviral integration oncogene spi1".
  4. (April 2023). "SWI/SNF Blockade Disrupts PU.1-Directed Enhancer Programs in Normal Hematopoietic Cells and Acute Myeloid Leukemia". Cancer Research.
  5. (July 2010). "The role of PU.1 and GATA-1 transcription factors during normal and leukemogenic hematopoiesis". Leukemia.
  6. (February 2019). "PU.1 controls fibroblast polarization and tissue fibrosis". Nature.
  7. (February 1998). "The transcription factor Spi-1/PU.1 interacts with the potential splicing factor TLS". The Journal of Biological Chemistry.
  8. (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.
  9. (February 1999). "Assembly requirements of PU.1-Pip (IRF-4) activator complexes: inhibiting function in vivo using fused dimers". The EMBO Journal.
  10. (July 2002). "Crystallization and characterization of PU.1/IRF-4/DNA ternary complex". Journal of Structural Biology.
  11. (May 1996). "The transcription factor Spi-1/PU.1 binds RNA and interferes with the RNA-binding protein p54nrb". The Journal of Biological Chemistry.

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transcription-factors