Cell cycle dependent histone dynamics of an episomal non-viral vector

Non-viral episomal vectors are regarded as attractive alternatives to currently used virus-based vectors in gene therapy. In addition, they represent a minimal model system to study the epigenetic control of basic nuclear processes, such as transcription, replication and nuclear retention. Here we analyze the dynamics of histone modifications during the cell cycle of the episomally replicating vector pEPI-eGFP. The histone code of pEPI-eGFP was compared to its integrating counterpart pGFP-C1. We found that pEPI-eGFP is preferentially associated with histone modifications typical for active chromatin, while pGFP-C1 is mostly decorated with repressive histone modifications. During interphase the distribution of histone modification on pEPI-eGFP is very non-dynamic; the S/MAR shows the highest concentration of active histone modifications. However, they are specifically removed during mitosis and this may correlate with the association and co-segregation of pEPI with the host chromosomes during cell division. (C) 2009 Elsevier B.V. All rights reserved.