Target DNA chromatinization modulates nicking by L1 endonuclease

L1 elements are human transposons which replicate via an RNA intermediate. At least 15% of the human genome is composed of L1 sequence. An important i nitial step in the transposition reaction is nicking of the genomic DNA by L1 endonuclease (L1 EN), In vivo much of the genome exists in the form of c hromatin or is undergoing biochemical transactions such as transcription, r eplication or repair, which may alter the accessibility of the L1 transposi tion machinery to DNA, To investigate this possibility we have examined the effect of substrate chromatinization on the ability of L1 EN to nick DNA, We find that DNA incorporated into nucleosomes is generally refractory to n icking by L1 EN, Interestingly, nicking of a minority of DNA sequences is e nhanced when included in chromatin, Thus, dynamic epigenetic factors such a s chromatinization are likely to influence the relatively permanent placeme nt of L1 and other retroelements in the human genome.