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The DNA-bending protein HMGB1 is a cellular cofactor of Sleeping Beauty transposition

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Item Type:Article
Title:The DNA-bending protein HMGB1 is a cellular cofactor of Sleeping Beauty transposition
Creators Name:Zayed, H. and Izsvak, Z. and Khare, D. and Heinemann, U. and Ivics, Z.
Abstract:Sleeping Beauty (SB) is the most active Tc1/ mariner-type transposon in vertebrates. SB contains two transposase-binding sites (DRs) at the end of each terminal inverted repeat (IR), a feature termed the IR/DR structure. We investigated the involvement of cellular proteins in the regulation of SB transposition. Here, we establish that the DNA-bending, high-mobility group protein, HMGB1 is a host-encoded cofactor of SB transposition. Transposition was severely reduced in mouse cells deficient in HMGB1. This effect was rescued by transient over-expression of HMGB1, and was partially complemented by HMGB2, but not with the HMGA1 protein. Over-expression of HMGB1 in wild-type mouse cells enhanced transposition, indicating that HMGB1 can be a limiting factor of transposition. SB transposase was found to interact with HMGB1 in vivo, suggesting that the transposase may recruit HMGB1 to transposon DNA. HMGB1 stimulated preferential binding of the transposase to the DR further from the cleavage site, and promoted bending of DNA fragments containing the transposon IR. We propose that the role of HMGB1 is to ensure that transposase-transposon complexes are first formed at the internal DRs, and subsequently to promote juxtaposition of functional sites in transposon DNA, thereby assisting the formation of synaptic complexes.
Keywords:Base Sequence, Binding Sites, Cell Line, DNA, DNA Transposable Elements, DNA-Binding Proteins, HMGB1 Protein, Macromolecular Substances, Insertional Mutagenesis, Nucleic Acid Conformation, Plasmids, Protein Binding, Terminal Repeat Sequences, Transfection, Transposases, Animals
Source:Nucleic Acids Research
Publisher:Oxford University Press
Page Range:2313-2322
Date:1 May 2003
Official Publication:https://doi.org/10.1093/nar/gkg341
PubMed:View item in PubMed

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