HMGB2 contains two basic DNA-binding domains, known as HMG-box A and B, and a C-terminal acidic tail . This structure allows HMGB2 to bind to non-canonical DNA structures such as single-stranded DNA, enhancing DNA flexibility by looping. This mechanism promotes activities on various gene promoters by enhancing transcription factor binding and/or bringing distant regulatory sequences into close proximity .
HMGB2 plays multiple roles in different cellular compartments. In the nucleus, it is involved in transcription, chromatin remodeling, and V(D)J recombination . It acts as a cofactor of the RAG complex, stimulating cleavage and RAG protein binding at the 23 bp spacer of conserved recombination signal sequences (RSS) . Additionally, HMGB2 is involved in the final ligation step in DNA end-joining processes of DNA double-strand breaks repair and V(D)J recombination .
Unlike HMGB1, which is ubiquitously expressed, HMGB2 expression is restricted mainly to lymphoid organs and testes, although it is widely expressed during embryogenesis . In human aortic smooth muscle cells, HMGB2 can enhance cell proliferation and migration by inducing reactive oxygen species . In vivo and in vitro analyses indicate that HMGB2 loss in cardiomyocytes causes hypertrophy and increased expression of genes responsible for hypertrophic cell growth .
HMGB2 has been associated with various diseases. For instance, it is linked to ceroid lipofuscinosis, neuronal, 6A . Studies have shown that HMGB2 plays a role in germ cell differentiation, as hmgb2−/− mice exhibit reduced fertility . Additionally, these mice possess reduced superficial zone cellularity and accelerated development of osteoarthritis .
Recombinant HMGB2 is produced using genetic engineering techniques, where the HMGB2 gene is cloned and expressed in suitable host cells. This allows for the production of large quantities of HMGB2 protein for research and therapeutic purposes. Recombinant HMGB2 retains the functional properties of the native protein, making it a valuable tool for studying its biological roles and potential therapeutic applications.