In genetics, transcriptional amplification is the process in which the total amounts of messenger RNA (mRNA) molecules from expressed genes are increased during disease, development, or in response to stimuli.
At the subset of genes expressed in a given cell, the transcribing activity of RNA Polymerase II results in mRNA production. Transcriptional amplification is specifically defined as the increase in per-cell abundance of this set of expressed mRNAs. Transcriptional amplification is caused by changes in the amount or activity of transcription-regulating proteins.
Gene expression is regulated by numerous types of proteins that directly or indirectly influence transcription by RNA Polymerase II. As opposed to transcriptional activators or repressors that selectively activate or repress specific genes, amplifiers of transcription act globally on the set of initially expressed genes.
Several known regulators of transcriptional amplification have been characterized including the oncogene Myc., the Rett syndrome protein MECP2, and the BET bromodomain protein BRD4. In particular, the Myc protein amplifies transcription by binding to promoters and enhancers of active genes where it directly recruits the transcription elongation factor P-TEFb. Furthermore, the BRD4 protein is a regulator of Myc activity.
Commonly used gene expression experiments interrogate the expression of one (qPCR) or many (microarray, RNA-Seq) genes. These techniques generally measure relative mRNA levels and employ normalization methods that assume only a small number of genes show altered expression. Instead, single cell or cell count normalized absolute measurements of mRNA abundance are required to reveal transcriptional amplification. Additionally, global measurements of mRNA or total mRNA per cell can also uncover evidence for transcriptional amplification.