Abstract
Simian virus 40 (SV40) early transcription is repressed when the product of early transcription, T-antigen, binds to its cognate regulatory sequence, Site I, in the promoter of the SV40 minichromosome. Because SV40 minichromosomes undergo replication and transcription potentially repression could occur during active transcription or during DNA replication. Since repression is frequently epigenetically marked by the introduction of specific forms of methylated histone H3, we characterized the methylation of H3 tails during transcription and replication in wild-type SV40 minichromosomes and mutant minichromosomes which did not repress T-antigen expression. While repressed minichromosomes following replication were clearly marked with H3K9me1 and H3K4me1, minichromosomes repressed during early transcription were not similarly marked. Instead repression of early transcription was marked by a significant reduction in the level of H3K9me2. The replication dependent introduction of H3K9me1 and H3K4me1 into wild-type SV40 minichromosomes was also observed when replication was inhibited with aphidicolin. The results indicate that the histone modifications associated with repression can differ significantly depending upon whether the chromatin being repressed is undergoing transcription or replication.
Highlights
The selective methylation of the amino terminal tails of histone H3 and H4, a well-known form of epigenetic regulation, has been associated with a number of important biological regulatory processes including the control of transcription and cellular differentiation (Atkinson et al, 2008; Corry et al, 2009; Bonasio et al, 2010; Gibney and Nolan, 2010; Lister et al, 2011; Shafa et al, 2011; Skinner, 2011)
We hypothesized that if transcriptional repression occurring at early times was associated with mono-methylation of H3K9 as observed during DNA replication, we would observe an increase in H3K9me1 over the first hours of an infection perhaps approaching the 20% value seen at late times when transcriptional repression was occurring
In Simian virus 40 (SV40) minichromosomes, repression of early gene expression by T-antigen binding to Site I in the viral regulatory region was shown to result in distinct epigenetic marks at early and late times post-infection
Summary
The selective methylation of the amino terminal tails of histone H3 and H4, a well-known form of epigenetic regulation, has been associated with a number of important biological regulatory processes including the control of transcription and cellular differentiation (Atkinson et al, 2008; Corry et al, 2009; Bonasio et al, 2010; Gibney and Nolan, 2010; Lister et al, 2011; Shafa et al, 2011; Skinner, 2011). Epigenetic regulation of transcription can occur either to control a particular gene’s expression during a cell’s life, or to pass along transcriptional information following cell division. The former would be an example of intragenerational epigenetic regulation while the latter would be an example of trans-generational regulation. A model for the inheritance of cellular transgenerational epigenetic information has emerged in which nucleosomes containing parental epigenetic information are randomly passed to daughter DNA during replication. These nucleosomes act to direct the modification of histones present in the newly replicated nucleosomes added to the DNA in order to conserve the parental epigenetic modifications in the daughter chromatin (Corpet and Almouzni, 2009; Zhu and Reinberg, 2011)
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
