BEND6 Human

BEN Domain Containing 6 (BEND6) is a neural BEN-solo factor that shares many functional attributes with Drosophila Insensitive, a co-repressor for the Drosophila CSL factor . This protein binds the mammalian CSL protein CBF1 and antagonizes Notch-dependent target activation . BEND6 is part of a family of proteins characterized by the presence of the BEN domain, a newly discovered type of DNA-binding domain .

The BEN domain is named after the exemplar proteins BANP, E5R, and NACC1 (also known as NAC1) . There are nine BEN domain-containing proteins in humans, including BANP, BEND2–7, NACC1, and NACC2 . These proteins have chromatin-related functions and are involved in DNA recognition and binding . BEND6, specifically, binds to the CSL protein CBF1 and antagonizes Notch-dependent target activation .

Recombinant human BEND6 protein is typically expressed in E. coli and purified using conventional chromatography techniques . The recombinant protein often includes a His-tag at the N-terminus to facilitate purification . The amino acid sequence of the recombinant human BEND6 protein includes several key regions that are essential for its function .

BEND6 plays a crucial role in neural development. In utero electroporation experiments have shown that ectopic BEND6 inhibits Notch-mediated self-renewal of neocortical neural stem cells and promotes neurogenesis . This indicates that BEND6 is essential for the proper differentiation of neural stem cells into neurons.

The DNA recognition mechanism of BEN domain proteins, including BEND6, involves binding to specific DNA sequences. Some BEN domain proteins, such as BANP and BEND3, preferentially bind to DNA bearing unmethylated CpG motifs . This binding is crucial for their function as CpG island-binding proteins . The crystal structures of BEN domains in complex with their cognate DNA substrates have revealed the details of DNA binding and the role of oligomerization in DNA selection .