EGR2

Description

The EGR2 (early growth response 2) is a protein-coding gene located on chromosome 10.

Early growth response protein 2 is a protein that in humans is encoded by the EGR2 gene. EGR2 (also termed Krox20) is a transcription regulatory factor, containing three zinc finger DNA-binding sites, and is highly expressed in a population of migrating neural crest cells. It is later expressed in the neural crest derived cells of the cranial ganglion. The protein encoded by Krox20 contains two cys2his2-type zinc fingers. Krox20 gene expression is restricted to the early hindbrain development. It is evolutionarily conserved in vertebrates, humans, mice, chicks, and zebra fish. In addition, the amino acid sequence and most aspects of the embryonic gene pattern is conserved among vertebrates, further implicating its role in hindbrain development. When the Krox20 is deleted in mice, the protein coding ability of the Krox20 gene (including the DNA-binding domain of the zinc finger) is diminished. These mice are unable to survive after birth and exhibit major hindbrain defects. These defects include but are not limited to defects in formation of cranial sensory ganglia, partial fusion of the trigeminal nerve (V) with the facial (VII) and auditory (VII) nerves, the proximal nerve roots coming off of these ganglia were disorganized and intertwined among one another as they entered the brainstem, and there was fusion of the glossopharyngeal (IX) nerve complex.

EGR2 is a sequence-specific DNA-binding transcription factor that plays a role in hindbrain segmentation by regulating the expression of a subset of homeobox containing genes. EGR2 also regulates the expression of genes involved in Schwann cell myelination, which is the process of forming and maintaining myelin. EGR2 binds to two consensus sites, EGR2A (5'-CTGTAGGAG-3') and EGR2B (5'-ATGTAGGTG-3'), in the HOXB3 enhancer, and promotes HOXB3 transcriptional activation. It also binds to specific DNA sites in the promoter region of HOXA4, HOXB2, and ERBB2. EGR2 regulates hindbrain segmentation by controlling the expression of Hox genes such as HOXA4, HOXB3, and HOXB2, thereby specifying odd and even rhombomeres. It promotes the expression of HOXB3 in the rhombomere r5 in the hindbrain. EGR2 regulates myelination in the peripheral nervous system after birth, possibly by regulating the expression of myelin proteins such as MPZ and by promoting the differentiation of Schwann cells. EGR2 is involved in the development of the jaw opener musculature, probably by playing a role in its innervation through trigeminal motor neurons. It may play a role in adipogenesis, possibly by regulating the expression of CEBPB.

EGR2 is also known as AT591, CMT1D, CMT4E, KROX20.

Associated Diseases

• Charcot-Marie-Tooth disease, demyelinating, type 1D
• Neuropathy, congenital hypomyelinating, 1, autosomal recessive
• Hypertrophic neuropathy of dejerine-sottas