Transcription factor PU.1 is a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...
that in humans is encoded by the ''SPI1''
gene
In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
.
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
Haematopoiesis (; ; also hematopoiesis in American English, sometimes h(a)emopoiesis) is the formation of blood cellular components. All cellular blood components are derived from haematopoietic stem cells. In a healthy adult human, roughly ten ...
and
cell fate decisions. PU.1 can physically interact with a variety of regulatory factors like
SWI/SNF
In molecular biology, SWI/SNF (SWItch/Sucrose Non-Fermentable), is a subfamily of ATP-dependent chromatin remodeling complexes, which is found in eukaryotes. In other words, it is a group of proteins that associate to remodel the way DNA is packa ...
,
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
Cytokines () are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling.
Cytokines are produced by a broad range of cells, including immune cells like macrophages, B cell, B lymphocytes, T cell, T lymphocytes ...
. It is expressed in
monocytes
Monocytes are a type of leukocyte or white blood cell. They are the largest type of leukocyte in blood and can differentiate into macrophages and monocyte-derived dendritic cells. As a part of the vertebrate innate immune system monocytes also i ...
,
granulocytes
Granulocytes are cells in the innate immune system characterized by the presence of specific granules in their cytoplasm. Such granules distinguish them from the various agranulocytes. All myeloblastic granulocytes are polymorphonuclear, that ...
,
B and
NK cells but is absent in
T cells,
reticulocytes
In hematology, reticulocytes are immature red blood cells (RBCs). In the process of erythropoiesis (red blood cell formation), reticulocytes develop and mature in the bone marrow and then circulate for about a day in the blood stream before ...
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 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
A lymphocyte is a type of white blood cell (leukocyte) in the immune system of most vertebrates. Lymphocytes include T cells (for cell-mediated and cytotoxic adaptive immunity), B cells (for humoral, antibody-driven adaptive immunity), and ...
. PU.1 induces the polarization of resting and inflammatory fibroblasts into 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:
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FUS,
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GATA2,
*
IRF4,
and
*
NONO.
References
Further reading
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External links
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{{Transcription factors
Transcription factors