Chapter 16: Promoter elements and alternative splicing in the human ACHE gene

Abstract

Publisher Summary A single gene mapped to the 7q22 chromosomal position encodes the ubiquitous acetylcholine hydrolysing enzyme acetylcholinesterase in humans. This unique locus must therefore direct the production of AChE in muscle and nerve, as well as in hemopoietic cells, embryonic tissues, different tumors, and germ cells. Furthermore, the ACHE gene must encode both the major hydrophilic form of AChE expressed in the brain and muscle and the hydrophobic, phosphoinositide (PI)-linked form of the enzyme found in erythrocytes. To reveal the molecular mechanisms underlying this heterogeneous expression, promoter elements and alternative splicing were investigated in the cloned human ACHE gene. The pleiotropic, developmentally-modulated expression and molecular polymorphism of AChE in humans may be attributed to transcriptional, post-transcriptional, and post-translational control mechanisms. These in turn depend on the functioning of multiple nuclear transcriptions and splicing factors and on the association of the different C-terminal peptides in the catalytic subunits with variable structural elements. Understanding of the molecular elements involved in this intricate expression pattern now provides the necessary tools to investigate the roles of AChE in mechanisms of cholinergic function and dysfunction.