The Myc oncoprotein represses initiator-dependent transcription through the POZ domain transcription factor Miz-1. We now show that transactivation by Miz-1 is negatively regulated by association with topoisomerase II binding protein (TopBP1); UV irradiation downregulates expression of TopBP1 and releases Miz-1. Miz-1 binds to the p21Cip1 core promoter in vivo and is required for upregulation of p21Cip1 upon UV irradiation. Using both c-myc(-/-) cells and a point mutant of Myc that is deficient in Miz-1 dependent repression, we show that Myc negatively regulates transcription of p21Cip1 upon UV irradiation and facilitates recovery from UV-induced cell cycle arrest through binding to Miz-1. Our data implicate Miz-1 in a pathway that regulates cell proliferation in response to UV irradiation.

Genome mining and chemical analyses revealed that rhizosphere bacteria (Paraburkholderia graminis) produce a new type of siderophore, gramibactin, a lipodepsipeptide that efficiently binds iron with a logβ value of 27.6. Complexation-induced proton NMR chemical shifts show that the unusual N-nitrosohydroxylamine (diazeniumdiolate) moieties participate in metal binding. Gramibactin biosynthesis genes are conserved in numerous plant-associated bacteria associated with rice, wheat, and maize, which may utilize iron from the complex.

Genomic sequencing was used to study the extent of cytosine methylation of four CpG sites within the regulatory region of the estradiol-inducible avian vitellogenin II gene. Three of these sites, two of which lie within the estradiol-receptor binding site and one in a short stretch of alternating purines and pyrimidines, were initially fully methylated. Analysis of DNA isolated from liver nuclei revealed that hormone treatment of immature White Leghorn roosters resulted in a demethylation of these sites, which occurred initially in only one DNA strand. This demethylation correlated well with the induction of vitellogenin mRNA synthesis. The demethylation of the complementary DNA strand lagged -24 hr behind. The fourth CpG, located within an overlapping glucocorticoid-receptor binding site, was already hemimethylated at the onset of the experiment. The demethylation of this site also occurred with kinetics similar to the rate of vitellogenin mRNA synthesis. All four CpGs remained demethylated even after cessation of gene transcription. A comparison of the methylation state of these four sites in DNA from different tissues demonstrated a clear dependence of the demethylation on estradiol. Our results suggest that this hormone-dependent event occurs via an active pathway through excision repair and/or enzymatic demethylation.

Both allo- and autotetraploidy induce considerable morphological, genetic and genomic changes, many of which are retained by at least one of the natural polyploids. It is proposed that both natural and synthetic polyploids are well suited for studying the evolution of adaptive responses.