Lee, Junghee Hwang, Yu Jin Shin, Jong-Yeon Lee, Won-Chul Wie, Jinhong Kim, Ki Yoon Lee, Min Young Hwang, Daehee Ratan, Rajiv R. Pae, Ae Nim Kowall, Neil W. So, Insuk Kim, Jong-Il Ryu, Hoon 2024-01-20T12:31:44Z 2024-01-20T12:31:44Z 2021-09-05 2013-05 0001-6322 https://pubs.kist.re.kr/handle/201004/128114 Huntington's disease (HD) is an autosomal dominant neurodegenerative disease caused by an expanded trinucleotide CAG repeat in the gene coding for huntingtin. Deregulation of chromatin remodeling is linked to the pathogenesis of HD but the mechanism remains elusive. To identify what genes are deregulated by trimethylated histone H3K9 (H3K9me3)-dependent heterochromatin, we performed H3K9me3-ChIP genome-wide sequencing combined with RNA sequencing followed by platform integration analysis in stable striatal HD cell lines (STHdhQ7/7 and STHdhQ111/111) cells. We found that genes involving neuronal synaptic transmission including cholinergic receptor M1 (CHRM1), cell motility, and neuronal differentiation pathways are downregulated while their promoter regions are highly occupied with H3K9me3 in HD. Moreover, we found that repression of CHRM1 gene expression by H3K9me3 impairs Ca2+-dependent neuronal signal transduction in stable cell lines expressing mutant HD protein. Thus, our data indicate that the epigenetic modifications, such as aberrant H3K9me3-dependent heterochromatin plasticity, directly contribute to the pathogenesis of HD. English SPRINGER STRIATAL CELLS H3 HETEROCHROMATIN METHYLATION EXPRESSION NEURONS ESET METHYLTRANSFERASE INTERNEURONS MODULATION Epigenetic regulation of cholinergic receptor M1 (CHRM1) by histone H3K9me3 impairs Ca2+ signaling in Huntington's disease Article 10.1007/s00401-013-1103-z 1 ACTA NEUROPATHOLOGICA, v.125, no.5, pp.727 - 739 ACTA NEUROPATHOLOGICA 125 5 727 739 scie scopus 000317923400009 2-s2.0-84886255831 Clinical Neurology Neurosciences Pathology Neurosciences & Neurology Pathology Article STRIATAL CELLS H3 HETEROCHROMATIN METHYLATION EXPRESSION NEURONS ESET METHYLTRANSFERASE INTERNEURONS MODULATION H3K9me3 Epigenomes Huntington&apos s disease Cholinergic receptor M1 Heterochromatin