EGR2

EGR2, or early growth response 2, is a gene that encodes a zinc finger transcription factor also known as Krox-20. It is a member of the EGR family (EGR1–EGR4) and functions as an immediate-early response gene. The EGR2 protein contains three C2H2-type zinc finger domains that enable sequence-specific DNA binding and transcriptional regulation.

Expression of EGR2 is detected in developing neural crest derivatives and in Schwann cells undergoing differentiation. In the peripheral nervous system, EGR2 acts as a master regulator of myelination: loss of EGR2 function in mice results in failed Schwann cell maturation and defective myelin formation. EGR2 directly or indirectly regulates a set of myelin genes, including MPZ (myelin protein zero), MBP (myelin basic protein), and PMP22, coordinating the production of the myelin sheath around peripheral nerves.

Regulation of EGR2 involves signaling pathways activated by axonal contact and growth factors. SOX10, another key Schwann cell transcription factor, cooperates with EGR2, and neuregulin-1 signaling can induce EGR2 expression during nerve development.

Clinical significance of EGR2 is underscored by reports of pathogenic variants associated with inherited peripheral neuropathies characterized by hypomyelination or demyelination, expanding the Charcot–Marie–Tooth disease spectrum. The phenotypes range from congenital hypomyelinating neuropathies to later-onset demyelinating forms, reflecting EGR2’s essential role in peripheral nerve myelination. EGR2 is conserved across vertebrates and has roles in development beyond the peripheral nervous system, illustrating its broad regulatory importance.