Transcription factor PU.1 is a protein that in humans is encoded by the SPI1 gene. [5]
Transcription factor PU.1 is a protein that in humans is encoded by the SPI1 gene. [5]
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]
The ETS domain is the DNA-binding module of PU.1 and other ETS-family transcription factors.
SPI1 has been shown to interact with:
Interleukin 11 is a protein that in humans is encoded by the IL11 gene.
Transcription factor Jun is a protein that in humans is encoded by the JUN gene. c-Jun, in combination with protein c-Fos, forms the AP-1 early response transcription factor. It was first identified as the Fos-binding protein p39 and only later rediscovered as the product of the JUN gene. c-jun was the first oncogenic transcription factor discovered. The proto-oncogene c-Jun is the cellular homolog of the viral oncoprotein v-jun. The viral homolog v-jun was discovered in avian sarcoma virus 17 and was named for ju-nana, the Japanese word for 17. The human JUN encodes a protein that is highly similar to the viral protein, which interacts directly with specific target DNA sequences to regulate gene expression. This gene is intronless and is mapped to 1p32-p31, a chromosomal region involved in both translocations and deletions in human malignancies.
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Mitogen-activated protein kinase 8 is a ubiquitous enzyme that in humans is encoded by the MAPK8 gene.
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Interferon regulatory factor 4 (IRF4) also known as MUM1 is a protein that in humans is encoded by the IRF4 gene. IRF4 functions as a key regulatory transcription factor in the development of human immune cells. The expression of IRF4 is essential for the differentiation of T lymphocytes and B lymphocytes as well as certain myeloid cells. Dysregulation of the IRF4 gene can result in IRF4 functioning either as an oncogene or a tumor-suppressor, depending on the context of the modification.
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ETS domain-containing protein Elk-4 is a protein that in humans is encoded by the ELK4 gene.
Transcription factor Spi-B is a protein that in humans is encoded by the SPIB gene.
Transcription factor MafK is a bZip Maf transcription factor protein that in humans is encoded by the MAFK gene.
ETS-related transcription factor Elf-4 is a protein that in humans is encoded by the ELF4 gene.
Transcription factor ETV7 is a protein that in humans is encoded by the ETV7 gene.
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