Molecular, Genetic, and Biochemical Nutrition Commons^™

Holocarboxylase Synthetase Represses Long Terminal Repeats Through Epigenetic Synergies Between Biotin And Methyl Donors, And Activates Immune Response By Catalyzing Biotinylation Of Heat Shock Protein 72, Jing Xue

College of Education and Human Sciences: Dissertations, Theses, and Student Research

Holocarboxylase synthetase (HLCS) is the sole human protein biotin ligase in the human proteome. Other than its role as a coenzyme to the five carboxylases in intermediary metabolism, HLCS and biotin are involved in epigenetic gene regulation and immune response. Previously, it was shown that (1) HLCS physically interacts with histone methyl transferase EHMT-1 which creates histone H3 lysine 9 methylation (H3K9me) marks and biotinylates lysine (K) 161 in EHMT-1, thereby strenghtening the HLCS/EHMT-1 interaction; (2) biotin depletion and HLCS knockdown cause a loss of H3K9me marks leading to de-repression of long terminal repeats (LTRs) and chromosomal abnormalities; and (3) …