PU.1/Spi1

SECTIONS

1 - Function
2 - Involvement in disease
3 - Sequence similarities
4 - Tissue specificity
5 - Cellular localization
6 - Alternative names
7 - Database links
8 - Target type
9 - Primary research area
10 - Molecular weight

Function

Pioneer transcription factor, which controls hematopoietic cell fate by decompacting stem cell heterochromatin and allowing other transcription factors to enter otherwise inaccessible genomic sites. Once in open chromatin, can directly control gene expression by binding genetic regulatory elements and can also more broadly influence transcription by recruiting transcription factors, such as interferon regulatory factors (IRFs), to otherwise inaccessible genomic regions (PubMed:23658224, PubMed:33951726). Transcriptionally activates genes important for myeloid and lymphoid lineages, such as CSF1R (By similarity). Transcriptional activation from certain promoters, possibly containing low affinity binding sites, is achieved cooperatively with other transcription factors. FCER1A transactivation is achieved in cooperation with GATA1 (By similarity). May be particularly important for the pro- to pre-B cell transition (PubMed:33951726). Binds (via the ETS domain) onto the purine-rich DNA core sequence 5'-GAGGAA-3', also known as the PU-box (PubMed:33951726). In vitro can bind RNA and interfere with pre-mRNA splicing (By similarity).

Involvement in disease

Agammaglobulinemia 10, autosomal dominant

AGM10

A form of agammaglobulinemia, a primary immunodeficiency characterized by profoundly low or absent serum antibodies and low or absent circulating B-cells due to an early block of B-cell development. Affected individuals develop severe infections in the first years of life.

None

The disease is caused by variants affecting the gene represented in this entry.

Sequence similarities

Belongs to the ETS family.

Tissue specificity

In the bone marrow, concentrated in hematopoietic stem cell, lymphoid progenitor, myeloid lineage (granulocyte macrophage progenitors, classical dendritic cells, monocytes) and B-cell clusters. Among B-cells, predominantly expressed in pre-B1 cells (PubMed:33951726). Expressed in germinal center B-cells (PubMed:23166356).