The TFDP1 gene coding for DP1, the heterodimeric partner of the transcription factor E2F, is a target of deregulated E2F.

The TFDP1 gene codes for the heterodimeric partner DP1 of the transcription factor E2F. E2F, principal target of the tumor suppressor pRB, plays central roles in cell proliferation by activating a group of growth-related genes. E2F also mediates tumor suppression by activating tumor suppressor genes such as ARF, an upstream activator of the tumor suppressor p53, when deregulated from pRB upon oncogenic changes. Among 8 E2F family members (E2F1∼E2F8), expression of activator E2Fs (E2F1∼E2F3a) is induced at the G1/S boundary of the cell cycle after growth stimulation by E2F itself. However, mechanisms regulating DP1 expression are not known. We show here that over-expression of E2F1 and forced inactivation of pRB, by adenovirus E1a, induced TFDP1 gene expression in human normal fibroblast HFFs, suggesting that the TFDP1 gene is a target of E2F. Serum stimulation of HFFs also induced TFDP1 gene expression, but with different kinetics from that of the CDC6 gene, a typical growth-related E2F target. Both over-expression of E2F1 and serum stimulation activated the TFDP1 promoter. We searched for E2F1-responsive regions by 5' and 3' deletion of the TFDP1 promoter and by introducing point mutations in putative E2F1-responsive elements. Promoter analysis identified several GC-rich elements, mutation of which reduced E2F1-responsiveness but not serum-responsiveness. ChIP assays showed that the GC-rich elements bound deregulated E2F1 but not physiological E2F1 induced by serum stimulation. These results suggest that the TFDP1 gene is a target of deregulated E2F. In addition, knockdown of DP1 expression by shRNA enhanced ARF gene expression, which is specifically induced by deregulated E2F activity, suggesting that activation of the TFDP1 gene by deregulated E2F may function as a failsafe feedback mechanism to suppress deregulated E2F and maintain normal cell growth in the event that DP1 expression is insufficient relative to that of its partner activator E2Fs. a maximum of 6 keywords: E2F, DP1, TFDP1 gene, pRB, gene expression.

Effect of Providing Information on Students' Knowledge and Concerns about Hydraulic Fracking.

Governmental agencies, regulators, health professionals, and the public are faced with understanding and responding to new development practices and conditions in their local and regional environment. While hydraulic fracking (fracking) for shale gas has been practiced for over 50 years in some states, it is a relatively recent event in the northeastern United States. Providing environmental health information to the public about fracking requires understanding both the knowledge base and the perceptions of the public. The knowledge, perceptions, and concerns of college students about fracking were examined. Students were interviewed at Rutgers University in New Jersey, a state without any fracking, although fracking occurs in nearby Pennsylvania. Objectives were to determine (1) knowledge about fracking, (2) rating of concerns, (3) trusted information sources, (4) importance of fracking relative to other energy sources, and (5) the effect of a 15-min lecture and discussion on these aspects. On the second survey, students improved on their knowledge (except the components used for fracking), and their ratings changed for some concerns, perceived benefits, and trusted information sources. There was no change in support for further development of natural gas, but support for solar, wind, and wave energy decreased. Data suggest that students' knowledge and perceptions change with exposure to information, but many of these changes were due to students using the Internet to look up information immediately after the initial survey and lecture. Class discussions indicated a general lack of trust for several information sources available on the Web.