Relationship between the structure and function of the transcriptional regulator E2A

E proteins are transcriptional regulators that regulate many developmental processes in animals and lymphocytosis and leukemia in Homo sapiens. In particular, E2A, a member of the E protein family, plays a major role in the transcriptional regulatory network that promotes the differentiation and development of B and T lymphocytes. E2A-mediated transcriptional regulation usually requires the formation of E2A dimers, which then bind to coregulators. In this review, we summarize the mechanisms by which E2A participates in transcriptional regulation from a structural perspective. More specifically, the C-terminal helix-loop-helix (HLH) region of the basic HLH (bHLH) domain first dimerizes, and then the activation domains of E2A bind to different coactivators or corepressors in different cell contexts, resulting in histone acetylation or deacetylation, respectively. Then, the N-terminal basic region (b) of the bHLH domain binds to or dissociates from a specific DNA motif (E-box sequence). Last, trans-activation or trans-repression occurs. We also summarize the properties of these E2A domains and their interactions with the domains of other proteins. The feasibility of developing drugs based on these domains is discussed.

Automated summary

E proteins, particularly E2A, play a vital role in the transcriptional regulatory network involved in the differentiation and development of B and T lymphocytes. E2A-mediated transcriptional regulation involves dimerization of the C-terminal HLH region, binding of activation domains to different coactivators or corepressors, and subsequent interaction of the N-terminal basic region with specific DNA motifs. These interactions lead to trans-activation or trans-repression, ultimately influencing histone acetylation and gene expression. The potential for developing drugs based on these regulatory domains is also discussed in this review.