Heterochromatin biology

National Institute Of Diabetes And Digestive And Kidney Diseases

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Abstract

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 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. Now we have found that the condensed structure is also disrupted in part when histone acetylation increases. We have also found that similar changes can be observed when the enzyme dicer is depleted. Our results show that mechanisms of maintenance of constitutive heterochromatin in vertebrates may use some of the same mechanisms used by fission yeast.