Association of CBP/p300 acetylase and thymine DNA glycosylase links DNA repair and transcription.

DNA repair in chromatin is subject to topological constraints, suggesting a requirement for chromatin modification and remodeling activities. Thymine DNA glycosylase (TDG) initiates repair of G/T and G/U mismatches, commonly associated with CpG islands, by removing thymine and uracil moieties. We report that TDG associates with transcriptional coactivators CBP and p300 and that the resulting complexes are competent for both the excision step of repair and histone acetylation.

Synergy between estrogen receptor alpha activation functions AF1 and AF2 mediated by transcription intermediary factor TIF2.

The activation function AF2 in the ligand-binding domain of estrogen receptors ER alpha and ER beta signals through the recruitment of nuclear receptor coactivators. Recent evidence indicates that coactivators, such as the transcription intermediary factor TIF2, also bind to and transactivate the N-terminal AF1 function of the two ERs. We have generated TIF2 mutant proteins that are deficient in either AF1 or AF2 interaction and use these mutants to investigate the relative contribution of both AFs to TIF2 recruitment and transactivation.

The KID Study VI: diabetic complications and associated diseases in younger type 2 diabetics still performing a profession. Prevalence and correlation with duration of diabetic state, BMI and C-peptide.

A sub-study evaluated 698 younger (54.5 +/- 6.9 years) type 2 diabetics of the KID Study participants to establish the prevalence of diabetic complications and associated diseases and their correlation with body mass index (BMI), duration of disease and to C-peptide levels.

Ligand-dependent activation of transcription in vitro by retinoic acid receptor alpha/retinoid X receptor alpha heterodimers that mimics transactivation by retinoids in vivo.

All-trans and 9-cis retinoic acids (RA) signals are transduced by retinoic acid receptor/retinoid X receptor (RAR/RXR) heterodimers that act as functional units controlling the transcription of RA-responsive genes. With the aim of elucidating the underlying molecular mechanisms, we have developed an in vitro transcription system using a chromatin template made up of a minimal promoter and a direct repeat with 5-spacing-based RA response element. RARalpha and RXRalpha were expressed in and purified from baculovirus-infected Sf9 cells, and transcription was carried out by using naked DNA or chromatin templates.

Retinoic acid receptors interact physically and functionally with the T:G mismatch-specific thymine-DNA glycosylase.

The pleiotropic effects of retinoids are mediated by nuclear receptors that are activated by 9-cis- or all-trans-retinoic acid to function as ligand-dependent transcription factors. In a yeast one-hybrid screen for proteins capable of interacting with native retinoic acid receptor (RAR), we have isolated the T:G mismatch-specific thymine-DNA glycosylase (TDG), which initiates the repair of T:G mismatches caused by spontaneous deamination of methylated cytosines. Here, we report that TDG can interact with RAR and the retinoid X receptor (RXR) in a ligand-independent manner, both in yeast and in vitro.

The yeast Ada complex mediates the ligand-dependent activation function AF-2 of retinoid X and estrogen receptors.

Nuclear receptors can function as ligand-inducible transregulators in both mammalian and yeast cells, indicating that important features of control of transcription have been conserved throughout evolution. Here, we report the isolation and characterization of a yeast protein that exhibits properties expected for a coactivator/mediator of the ligand-dependent activation function AF-2 present in the ligand-binding domain (LBD, region E) of the retinoid X (RXRalpha) and estrogen (ERalpha) receptors. This protein is identical to Ada3, a component of the yeast Ada coactivator complex.

Delayed fetal development in two models of disturbed pregnancy of rats. Effect on mortality, body mass development, blood urea nitrogen (BUN) and urinary ammonium concentrations during the first week of extrauterine life.

To induce pregnancy disturbance, two models were used ("endotoxin-model" and "stress-model"), both causing decreased fetal body mass. Fetuses were delivered by Caesarean section in the morning of the 21st gestational day. Postnatal mortality rate during rearing for one week amounted to 12% in controls and was enhanced in the endotoxin- and stress-models (to approximately 25% and approximately 30%, respectively).