Nucleolar dominance is an epigenetic phenomenon that describes nucleolus formation around rRNA genes inherited from only one progenitor of an interspecific hybrid or allopolyploid. The phenomenon is widespread, occurring in plants, insects, amphibians, and mammals, yet its molecular basis remains unclear. We have demonstrated nucleolar dominance in three allotetraploids of the plant genus Brassica. In Brassica napus, accurately initiated pre-rRNA transcripts from one progenitor, Brassica rapa are detected readily, whereas transcripts from the ∼3000 rRNA genes inherited from the other progenitor, Brassica oleracea, are undetectable. Nuclear run-on confirmed that dominance is controlled at the level of transcription. Growth of B. napus seedlings on 5-aza-2-deoxycytidine to inhibit cytosine methylation caused the normally silent, under-dominant B. oleracea rRNA genes to become expressed to high levels. The histone deacetylase inhibitors sodium butyrate and trichostatin A also de-epressed silent rRNA genes. These results reveal an enforcement mechanism for nucleolar dominance in which DNA methylation and histone modifications combine to regulate rRNA gene loci spanning tens of megabase pairs of DNA.

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The level and activity of the forkhead family transcription factor FOXP3 determine the immune function of FOXP3+Tregs. At the beginning of infectious processes, FOXP3+Tregs may regulate effector immune cell responses and lead to failure to control infection. FOXP3+Tregs may also help to limit collateral tissue damage when the antiviral immune responses are too vigorous. Understanding the regulation of FOXP3 and the dynamic ensemble of FOXP3 with enzymatic cofactors in Tregs will provide therapeutic applications for major human viral infectious diseases including HIV, hepatitis B and C viruses.How FOXP3 protein is negatively regulated in CD4+ regulatory T cells during viral infection and inflammation is currently unknown. Here we report that a stresssignal activated E3 ubiquitin ligase STUB1 appears as a negative regulator of FOXP3. Reciprocal co-immunoprecipitation studies indicate that STUB1 interacts with FOXP3 in vivo. Overexpression of STUB1 specifically promotes the ubiquitination of FOXP3, but not other subfamily transcription factor FOXP1. MG132 treatment increased the ubiquitination level of FOXP3, and overexpression of STUB1 induced ubiquitin-mediated degradation of FOXP3. In contrast to the wild type STUB1, ectopic expression of H260Q mutant STUB1, which disrupts its interaction with E2 conjugation enzymes, didn't lead to FOXP3 degradation. Thus, FOXP3 degradation is mediated by enzymatically active STUB1. Moreover, FOXP3 degradation by STUB1 is also depend on its chaperoned binding, since overexpression of the K30A mutant of STUB1, which is incapable of interacting with chaperone proteins, also fails to promote FOXP3 degradation. Knockdown of endogenous STUB1 by shRNA could increase FOXP3 level in FOXP3 expressing T cells. Functionally, ectopic expression of STUB1 dramatically relieves FOXP3 mediated transcriptional suppression. Our studies identified a novel signal pathway to downregulate FOXP3 activity at posttranslational level by ubiquitin mediated protein degradation.