Ribosomal transcription in mammals is regulated in response to growth, differentiation, disease, and aging, but the mechanisms of this regulation have remained unresolved. We show that epidermal growth factor induces immediate, ERK1/2-dependent activation of endogenous ribosomal transcription, while inactivation of ERK1/2 causes an equally immediate reversion to the basal transcription level. ERK1/2 was found to phosphorylate the architectural transcription factor UBF at amino acids 117 and 201 within HMG boxes 1 and 2, preventing their interaction with DNA. Mutation of these sites inhibited transcription activation and abrogated the transcriptional response to ERK1/2. Thus, growth factor regulation of ribosomal transcription likely acts by a cyclic modulation of DNA architecture. The data suggest a central role for ribosome biogenesis in growth regulation.

The fatty acid composition, total trans content (i.e., sum of all the fatty acids which may have one or more trans double bonds) and geometric and positional isomer distribution of unsaturated fatty acids of 198 human milk samples collected in 1992 from nine provinces of Canada were determined using a combination of capillary gas-liquid chromatography and silver nitrate thin-layer chromatography. The mean total trans fatty acid content was 7.19 +/- 3.03% of the total milk fatty acids and ranged from 0.10 to 17.15%. Twenty-five of the 198 samples contained more than 10% total trans fatty acids, and thirteen samples contained less than 4%. Total trans isomers of linoleic acid were 0.89% of the total milk fatty acids with 18:2 delta 9c,13t being the most prevalent isomer, followed by 18:2 delta 9c,12t and 18:2 delta 9t,12c. Using the total trans values in human milk determined in the present study, the intake of total trans fatty acids from various dietary sources by Canadian lactating women was estimated to be 10.6 +/- 3.7 g/person/d, and in some individuals, the intake could be as high as 20.3 g/d. The 18:1 trans isomer distribution differed from that of cow's milk fat but was remarkably similar to that in partially hydrogenated soybean and canola oils, suggesting that partially hydrogenated vegetable oils are the major source of these trans fatty acids.

RNA polymerase I (PolI) transcription is activated by the HMG box architectural factor UBF, which loops approximately 140 bp of DNA into the enhancesome, necessitating major chromatin remodeling. Here we show that the acetyltransferase CBP is recruited to and acetylates UBF both in vitro and in vivo. CBP activates PolI transcription in vivo through its acetyltransferase domain and acetylation of UBF facilitates transcription derepression and activation in vitro. CBP activation and Rb suppression of ribosomal transcription by recruitment to UBF are mutually exclusive, regulating in vivo PolI transcription through an acetylation-deacetylation "flip-flop." Thus, PolI transcription is regulated by protein acetylation, and the competitive recruitment of CBP and Rb.