Biotinylation of histones represses transposable elements in human and mouse cells and cell lines and in Drosophila melanogaster.
Transposable elements such as long terminal repeats (LTR) constitute approximately 45% of the human genome; transposition events impair genome stability. Fifty-four promoter-active retrotransposons have been identified in humans. Epigenetic mechanisms are important for transcriptional repression of retrotransposons, preventing transposition events, and abnormal regulation of genes. Here, we demonstrate that the covalent binding of the vitamin biotin to lysine-12 in histone H4 (H4K12bio) and lysine-9 in histone H2A (H2AK9bio), mediated by holocarboxylase synthetase (HCS), is an epigenetic mechanism to repress retrotransposon transcription in human and mouse cell lines and in primary cells from a human supplementation study. Abundance of H4K12bio and H2AK9bio at intact retrotransposons and a solitary LTR depended on biotin supply and HCS activity and was inversely linked with the abundance of LTR transcripts. Knockdown of HCS in Drosophila melanogaster enhances retrotransposition in the germline. Importantly, we demonstrated that depletion of H4K12bio and H2AK9bio in biotin-deficient cells correlates with increased production of viral particles and transposition events and ultimately decreases chromosomal stability. Collectively, this study reveals a novel diet-dependent epigenetic mechanism that could affect cancer risk.
Chew
Yap Ching
YC
Department of Nutrition and Health Sciences, University of Nebraska, Lincoln, NE 68583, USA.
West
John T
JT
Kratzer
Stephanie J
SJ
Ilvarsonn
Anne M
AM
Eissenberg
Joel C
JC
Dave
Bhavana J
BJ
Klinkebiel
David
D
Christman
Judith K
JK
Zempleni
Janos
J
D000328:Adult; D000818:Animals; D001710:Biotin / Q000008:administration & dosage; D019921:Biotinylation; D019731:Carbon-Nitrogen Ligases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D002869:Chromosome Aberrations; D003596:Cytosine / Q000378:metabolism; D019175:DNA Methylation; D004251:DNA Transposable Elements; D019587:Dietary Supplements; D004331:Drosophila melanogaster; D044127:Epigenesis, Genetic; D005260:Female; D006657:Histones / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D019169:Jurkat Cells; D008297:Male; D008324:Mammary Tumor Virus, Mouse / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008875:Middle Aged; D012097:Repressor Proteins / Q000737:chemistry / Q000378:metabolism; D020079:Terminal Repeat Sequences; D014158:Transcription, Genetic / Q000187:drug effects; D019065:Virus Assembly / Q000187:drug effects; D055815:Young Adult
D004251:DNA Transposable Elements; D006657:Histones; D012097:Repressor Proteins; D001710:Biotin; D003596:Cytosine; D019731:Carbon-Nitrogen Ligases; C023312:holocarboxylase synthetases