MORC2
Description
The MORC2 (MORC family CW-type zinc finger 2) is a protein-coding gene located on chromosome 22.
MORC family CW-type zinc finger protein 2 is a protein that in humans is encoded by the MORC2 gene.
MORC2 is essential for epigenetic silencing mediated by the HUSH (human silencing hub) complex. It is recruited to target sites in heterochromatin by HUSH, and its ATPase activity and homodimerization are crucial for this silencing process. MORC2 collaborates with SETDB1 and HUSH to repress germ cell-related genes and L1 retrotransposons, relying on repressive epigenetic modifications like the H3K9me3 mark. Silencing often occurs within introns of transcriptionally active genes, leading to downregulation of the host gene expression. During DNA damage response, MORC2 regulates chromatin remodeling through ATP hydrolysis. Upon DNA damage, it is phosphorylated by PAK1, both colocalizing to chromatin and inducing H2AX expression. Its ATPase activity is required and dependent on phosphorylation by PAK1 and the presence of DNA. MORC2 recruits histone deacetylases like HDAC4 to promoter regions, causing local histone H3 deacetylation and transcriptional repression of genes such as CA9. In the cytosol, MORC2 plays a role in lipogenesis, adipogenic differentiation, and lipid homeostasis by increasing ACLY activity, possibly preventing its dephosphorylation.
MORC2 is also known as CMT2Z, DIGFAN, ZCW3, ZCWCC1.
Associated Diseases
- Autosomal dominant Charcot-Marie-Tooth disease type 2Z
- Developmental delay, impaired growth, dysmorphic facies, and axonal neuropathy
- Charcot-Marie-Tooth disease, axonal, type 2Z
