XB-ART-35076Pharmacol Ther. December 1, 2006; 26 (23): 9045-59.
The LRS and SIN domains: two structurally equivalent but functionally distinct nucleosomal surfaces required for transcriptional silencing.
Genetic experiments have identified two structurally similar nucleosomal domains, SIN and LRS, required for transcriptional repression at genes regulated by the SWI/SNF chromatin remodeling complex or for heterochromatic gene silencing, respectively. Each of these domains consists of histone H3 and H4 L1 and L2 loops that form a DNA-binding surface at either superhelical location (SHL) +/-2.5 (LRS) or SHL +/-0.5 (SIN). Here we show that alterations in the LRS domain do not result in Sin(-) phenotypes, nor does disruption of the SIN domain lead to loss of ribosomal DNA heterochromatic gene silencing (Lrs(-) phenotype). Furthermore, whereas disruption of the SIN domain eliminates intramolecular folding of nucleosomal arrays in vitro, alterations in the LRS domain have no effect on chromatin folding in vitro. In contrast to these dissimilarities, we find that the SIN and LRS domains are both required for recruitment of Sir2p and Sir4p to telomeric and silent mating type loci, suggesting that both surfaces can contribute to heterochromatin formation. Our study shows that structurally similar nucleosomal surfaces provide distinct functionalities in vivo and in vitro.
PubMed ID: 17015465
PMC ID: PMC1636829
Article link: Pharmacol Ther.
Grant support: GM 54096 NIGMS NIH HHS , GM 62385 NIGMS NIH HHS , R01 GM054096 NIGMS NIH HHS , R01 GM062385 NIGMS NIH HHS , GM 54096 NIGMS NIH HHS , GM 62385 NIGMS NIH HHS