A recent unexpected discovery that resulted from application of the chromatin immunoprecipitation technique (see Figure 9-18) is that a large fraction of genes in metazoans have a paused elongating RNA polymerase II within about 100 bp of the transcription start site. Thus expression of the encoded protein is controlled not only by transcription initiation, but also by transcription elongation early in the transcription unit. The first genes discovered to be regulated by control of transcription elongation were heat-shock genes (e.g., hsp70), which encode molecular chaperones that help to refold denatured proteins and other proteins that help the cell to deal with the effects of heat shock. When heat shock occurs, the heat-shock transcription factor (HSTF) is activated. Binding of activated HSTF to specific sites in the promoter-proximal region of heat-shock genes stimulates the paused polymerase to continue chain elongation and promotes rapid reinitiation by additional Pol II molecules, leading to many transcription initiations per minute. This mechanism of transcriptional control permits a rapid response: these genes are always paused in a state of suspended transcription and therefore, when an emergency arises, no time is required to remodel and acetylate chromatin at the promoter and assemble a transcription preinitiation complex.

Another transcription factor shown to regulate transcription by controlling elongation by Pol II paused near the transcription start site is MYC, which functions in the regulation of cell growth and division. MYC is often expressed at high levels in cancer cells and is a key transcription factor in the reprogramming of somatic cells into pluripotent stem cells capable of differentiation into any cell type. The ability to induce differentiated cells to convert to pluripotent stem cells has elicited enormous research interest because of its potential for the development of therapeutic treatments for traumatic injuries to the nervous system and degenerative diseases (see Chapter 21).