We are studying the mechanisms that maintain constitutive heterochromatic regions in a condensed form. For this purpose we are using a well characterized 16 kb heterochromatin segment located upstream of the chicken beta globin locus. In other published studies we have measured the hydrodynamic properties of this fragment, which is typical of a large proportion of vertebrate genomes, and which has the potential if unregulated to silence adjacent genes in a manner deleterious to cellular function. We have now found that maintenance of the condensed structure is coupled to low level transcription in the region, and that elevation of levels of histone acetylation by use of histone deacetylase inhibitors markedly increases transcription. We are presently investigating the relationship of this behavior to the mechanisms of heterochromatin stabilization recently established in fission yeast. We have found conditions in vivo under which we can disrupt the condensed structure.
| Ghirlando, Rodolfo; Felsenfeld, Gary (2008) Hydrodynamic studies on defined heterochromatin fragments support a 30-nm fiber having six nucleosomes per turn. J Mol Biol 376:1417-25 |
