Methylation and expression of neurofilament genes in tissues and in cell lines of the mouse.

The light (NF-L), mid-sized (NF-M) and heavy (NF-H) neurofilament (NF) genes were probed with methylation-sensitive restriction enzymes and patterns of methylation and expression of the NF genes were compared in tissues and cell lines of the mouse. The 5' regions of all three NF genes are identified as CpG islands that remain unmethylated in expressing and non-expressing tissues, although partial methylation occurs at -795 in NF-H and at -525 in NF-M. Methylation of the NF CpG islands is associated with the inactivation of NF genes in L cells and with the selective inactivation of NF-L and NF-M in Neuro 2a cells. We also show that methylation diminishes the ability of the NF promoters to drive transcription of a CAT reporter gene. Hence, the presence of CpG islands may be important in determining patterns of NF transcription in vitro. Moreover, the preservation of CpG islands may be an evolutionary link that bears upon the nature of the NF genes and the mechanisms that have evolved to limit NF expression.