Myrf

Myrf, short for myelin regulatory factor, refers to a transcription factor essential for the development of myelin in the central nervous system. In humans, the gene is known as MYRF. The protein is produced as a membrane-bound transcription factor anchored in the endoplasmic reticulum, containing a DNA-binding domain in its N-terminal region and a C-terminal portion that tethers it to the membrane. Through autoproteolytic cleavage, MYRF releases the N-terminal fragment, which can enter the nucleus and regulate gene expression.

Functionally, MYRF is expressed in oligodendrocyte lineage cells, including oligodendrocyte precursor cells and mature oligodendrocytes. It acts cell-autonomously to promote the initiation and progression of CNS myelination by activating transcription of myelin-related genes. Experimental models where MYRF function is disrupted show impaired expression of myelin-associated genes and defective CNS myelination, underscoring its critical regulatory role.

Clinical relevance for MYRF comes from observations that rare variants in the gene are associated with human demyelinating or hypomyelinating phenotypes in some individuals. The full clinical spectrum and penetrance of MYRF-related disorders are still being delineated, with ongoing research in both human patients and animal models to clarify how different mutations affect myelination and development.

Evolutionarily, MYRF is conserved across vertebrates and exemplifies a class of membrane-bound transcription factors that couple protein cleavage with nuclear gene regulation. This mechanism allows coordinated control of oligodendrocyte differentiation and CNS myelination during development.

See also: Oligodendrocyte, Myelin, Myelin basic protein, Oligodendrocyte precursor cell, Transcription factor.