Fig. 4.

A scheme represents an epigenetic mechanism that abnormal activity of histone H3K9-specific methyltransferase (ESET) leads to synaptic failure and striatal dysfunction in Huntingdon’s disease (HD). ESET-induced and H3K9me3-mediated heterochromatin condensation results in the repression of the CHRM1 gene and subsequent reduction of CHRM1 protein in medium spiny neurons (MSNs). Down-regulation of CHRM1 fails to respond to acetylcholine (Ach) from cholinergic interneurons and to transduce the G-protein-coupled intracellular Ca²⁺-dependent signaling pathway, which affects on the synaptic function of MSNs. Consequently, deregulation of CHRM1-dependent striatal synaptic function contributes to neurodegeneration in HD. This figure is reproduced from [69]. PLC = phospholipase C; Ins(1,4,5)P₃ = inositol 1,4,5-triphosphate; ER = endoplasmic reticulum