CHD2 and Associated Diseases
CHD2 and its encoded protein regulate gene expression in organisms by affecting the process of chromatin remodeling.
Structure and Function of CHD2
The chromatin domain helicase DNA-binding proteins (CHDs) family is characterized by that all subunits contain two chromatin structures that act as modifiers of chromatin organization and two helicase domains. As a class I CHD, CHD2 also includes a domain with an unknown function and several small domains (ADA2, N-COR, SWI3, and SANT). The N-terminus of CHD2 contains tandem chromatin domains responsible for the autoinhibition of DNA binding and ATPase activity.
The CHD2 gene encodes a chromatin remodeling enzyme called chromodomain-helicase-DNA-binding protein 2, which unifies the capabilities of ATP hydrolysis and DNA conformational changes, directly controls RNA polymerase-mediated transcription, and regulates eukaryotic chromatin structure and gene spatiotemporal expression in organisms.
CHD2 has many important functions in normal cells, including recognition of the H3K4me mark and deposition of the histone variant H3.3 as an epigenetic signal, assembly of nucleosomes, repair of DNA damage, regulation of gene expression processes, and control of complex tissue development. In addition, studies have also shown that CHD2 plays an important role in the development of neurons.
Fig 1. CHD2 gene and common mutation sites. (Chen, 2019)
CHD2 in Myelopoiesis and Hematopoiesis
Histological studies of the livers of neonatal mice demonstrate the impact of CHD2 mutations on the hematopoietic lineage. As a regulator of megakaryocyte development, CHD2 is essential for the process of myeloid differentiation. CHD2 heterozygous mutant mice died of multiple lymphomas and lymphoid hyperplasia, which defines the role of CHD2 derangement in hematological malignancies.
CHD2 in Tissue Development
CHD2 has been shown to play a key role in the development of many tissues, and CHD2-mutated mice have significantly reduced body weight at different developmental stages and also exhibited higher early lethality. Mutations in the CHD2 gene can also have malignant effects on brain development, memory formation, and spine & heart growth.
CHD2 and Neurological Disease
Current research has demonstrated the relationship between at least 30 CHD2 mutations and epilepsy, abnormal brain function, and mental retardation. More than half of the mutations delete stretches of CHD2 DNA and result in the absence or defective versions of the CHD2 protein that are not functional, and damage occurs primarily through a reduction in the ability of the CHD2 protein to remodel chromatin. In addition to the common developmental epileptic encephalopathy, CHD2 mutations can also lead to Sifrim-Hitz-Weiss syndrome, cognitive slowing or degeneration, light sensitivity, intellectual disability, or autism.
Fig 2. CHD2 regulates the proliferation of neural progenitors during forebrain development. (Kim, 2018)
Although the effects of CHD2 mutations on gene expression and protein products have been demonstrated, it is still unclear why CHD2 gene mutations almost exclusively affect nerve cells in the central nervous system, nor the downstream molecular mechanisms in this process. In response to this setback, Creative Biolabs provides one-stop solution services for CHD2 and its related diseases. Our service includes but is not limited to disease model construction, gene manipulation, mutation annotation, genome sequencing, and various molecular biology assays. We will be your best assistant to advance your research plan and help you complete any downstream testing required by your project.
References
- Kim, Y.J.; et al. CHD2 is necessary for neural circuit development and long-term memory. Neuron, 2018, 100(5): 1180-1193.
- Chen, J.Y.; et al. CHD2-related epilepsy: novel mutations and new phenotypes. Developmental Medicine & Child Neurology, 2019, 10: 647-653.
