E2A

E2A, also known as E2A transcription factor or by its gene name TCF3, refers to a family of basic helix-loop-helix (bHLH) transcription factors that play key roles in vertebrate development and hematopoiesis. In humans, the TCF3 gene is located on chromosome 19p13.3 and encodes multiple protein products that regulate gene expression by binding to E-box DNA motifs (CANNTG).

TCF3 is alternatively spliced to produce several isoforms, with E12 and E47 being the canonical products. These isoforms share the common bHLH domain but differ at their N-terminal regions, conferring distinct transactivation properties. E2A proteins form homodimers or heterodimers with other bHLH factors, enabling versatile regulation of target genes.

Functionally, E2A is essential for lymphoid development, particularly in B-cell lineage commitment. It promotes the expression of genes necessary for B-cell specification, including EBF1 and Pax5, and collaborates with other transcription factors to drive differentiation. E2A also participates in other developmental programs, including myogenesis and neurogenesis, through interactions with lineage-specific partners.

E2A activity is modulated by inhibitory Id proteins, which can bind E2A and prevent DNA binding, as well as by post-translational modifications that affect activity and stability. Dysregulation of E2A function is associated with oncogenesis; most notably, the t(1;19) chromosomal translocation creates an E2A-PBX1 fusion gene linked to pediatric acute lymphoblastic leukemia, illustrating a gene–fusion mechanism in cancer.