CBFB

The protein encoded by this gene is the beta subunit of a heterodimeric core-binding transcription factor belonging to the PEBP2/CBF transcription factor family which master-regulates a host of genes specific to hematopoiesis (e.g., RUNX1) and osteogenesis (e.g., RUNX2). The beta subunit is a non-DNA binding regulatory subunit; it allosterically enhances DNA binding by alpha subunit as the complex binds to the core site of various enhancers and promoters, including murine leukemia virus, polyomavirus enhancer, T-cell receptor enhancers and GM-CSF promoters. Alternative splicing generates two mRNA variants, each encoding a distinct carboxyl terminus. In some cases, a pericentric inversion of chromosome 16 [inv(16)(p13q22)] produces a chimeric transcript consisting of the N terminus of core-binding factor beta in a fusion with the C-terminal portion of the smooth muscle myosin heavy chain 11. This chromosomal rearrangement is associated with acute myeloid leukemia of the M4Eo subtype. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

Full Name

CBFB

Function

Forms the heterodimeric complex core-binding factor (CBF) with RUNX family proteins (RUNX1, RUNX2, and RUNX3). RUNX members modulate the transcription of their target genes through recognizing the core consensus binding sequence 5'-TGTGGT-3', or very rarely, 5'-TGCGGT-3', within their regulatory regions via their runt domain, while CBFB is a non-DNA-binding regulatory subunit that allosterically enhances the sequence-specific DNA-binding capacity of RUNX. The heterodimers bind to the core site of a number of enhancers and promoters, including murine leukemia virus, polyomavirus enhancer, T-cell receptor enhancers, LCK, IL3 and GM-CSF promoters. CBF complexes repress ZBTB7B transcription factor during cytotoxic (CD8+) T cell development. They bind to RUNX-binding sequence within the ZBTB7B locus acting as transcriptional silencer and allowing for cytotoxic T cell differentiation.

Biological Process

Cell maturation Source: Ensembl
Definitive hemopoiesis Source: Ensembl
Lymphocyte differentiation Source: Ensembl
Myeloid cell differentiation Source: Ensembl
Negative regulation of CD4-positive, alpha-beta T cell differentiation Source: UniProtKB
Negative regulation of transcription by RNA polymerase II Source: UniProtKB
Osteoblast differentiation Source: Ensembl
Positive regulation of CD8-positive, alpha-beta T cell differentiation Source: UniProtKB
Positive regulation of transcription by RNA polymerase II Source: Ensembl
Protein polyubiquitination Source: CACAO
Regulation of B cell receptor signaling pathway Source: Reactome
Regulation of bicellular tight junction assembly Source: Reactome
Regulation of cytokine-mediated signaling pathway Source: Reactome
Regulation of hematopoietic stem cell differentiation Source: Reactome
Regulation of intracellular estrogen receptor signaling pathway Source: Reactome
Regulation of keratinocyte differentiation Source: Reactome
Regulation of megakaryocyte differentiation Source: Reactome
Regulation of myeloid cell differentiation Source: Reactome
Regulation of regulatory T cell differentiation Source: Reactome
Regulation of transcription by RNA polymerase II Source: GO_Central
Regulation of transcription initiation from RNA polymerase II promoter Source: Reactome
Regulation of Wnt signaling pathway Source: Reactome
Transcription by RNA polymerase II Source: ProtInc

Cellular Location

Nucleus

Involvement in disease

A chromosomal aberration involving CBFB is associated with acute myeloid leukemia of M4EO subtype. Pericentric inversion inv(16)(p13;q22). The inversion produces a fusion protein that consists of the 165 N-terminal residues of CBF-beta (PEPB2) with the tail region of MYH11.