Elsevier

The Journal of Nutrition

Volume 138, Issue 12, December 2008, Pages 2316-2322
The Journal of Nutrition

Biotinylation of Histones Represses Transposable Elements in Human and Mouse Cells and Cell Lines and in Drosophila melanogaster123

https://doi.org/10.3945/jn.108.098673Get rights and content
Under an Elsevier user license
open archive

Abstract

Transposable elements such as long terminal repeats (LTR) constitute ∼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.

Abbreviations

AZA
5-aza-2´-deoxycytidine
ChIP
chromatin immunoprecipitation
HCS
holocarboxylase synthetase
H3-C
C terminus in human histone H3
H3K4me3
K4-trimethylated histone H3
H4K8bio
K8-biotinylated histone H4
H2AK9bio
K9-biotinylated histone H2A
H3K9me2
K9-dimethylated histone H3
H4K12bio
K12-biotinylated histone H4
H2AK13bio
K13-biotinylated histone H2A
LINE
long interspersed nucleotide elements
LTR
long terminal repeat
MMTV
mouse mammary tumor virus

Cited by (0)

1

Supported in part by funds provided through the Hatch Act. A contribution of the University of Nebraska Agricultural Research Division. Additional support was provided by NIH grants DK 063945 and ES 015206, USDA grant 2006-35200-17138, National Science Foundation EPSCoR grant EPS-0701892, and National Science Foundation grant MCB 0615831.

2

Author disclosures: Y. Chew, J. West, S. Kratzer, A. Ilvarsonn, J. Eissenberg, B. Dave, D. Klinkebiel, J. Christman, and J. Zempleni, no conflicts of interest.