Abstracts of the Plenary and Symposia Talks; and Poster Presentations

摘要

Differential regulation of gene expression is the underlying mechanism involved in development and disease. During cardiac hypertrophy there are two distinct gene expression changes that occur in the myocyte. One is the total increase in cellular mRNA and protein that is commensurate with, and responsible for, the increase in cell mass and volume (∼30%). The second is selective, more dramatic, increases or decreases in specific genes that play a more specialized role in cell growth. Until recently it was assumed that transcriptional activation of genes is achieved by de novo recruitment of RNA polymerase II to promoters. However, this idea has recently been challenged by studies in Drosophila, which suggest that RNA polymerase II (pol II) is already bound to the promoter-proximal region of a gene. To understand the full nature of these transcriptional activities, we examined the RNA pol II bound to the genome before and after development of hypertrophy in a genome-wide approach. This was accomplished by pol II chromatin immunoprecipitation followed by extensive sequencing (ChIP-Seq). The results of this were aligned to the genome and viewed in both a quantitative and qualitative graphical format with Affymetrix’ Integrated Genome Browser software. Our results with poll ChIP-Seq not only identify widespread promoter-proximal RNA pol II pausing in the adult heart, but also reveal its synchronized release during cardiac hypertrophy, which recapitulates the neonatal heart pattern. We have also uncovered a unique aspect of RNA pol II transcription that has never been seen before, in the form of its stalling as it exits the gene’s 3’ boundary. The data provide unique mechanistic insights into the regulation of gene transcription during hypertrophy.