Transcribed enhancers lead waves of coordinated transcription in transitioning mammalian cells
33. The use of microarray data sets to identify alternative mechanisms of TERT reactivation employed by those cell lines that were WT at positions -124 and -146 was unsuccessful. Average mRNA levels were roughly similar for (i) the ETS1 and ETS2 transcription factors (~1.1-fold higher in the WT group), (ii) the c-MYC transcription factor (~1.4-fold higher in the WT group), and (iii) the core components of the Polycomb repressive complex 2 (between~0.91-fold and~1.3-fold higher in the WT group).
... 34. J. Nandakumar et al., Nature 492, 285-289 (2012). ACKNOWLEDGMENTS We thank C. Owens for providing the UC23, as well as detailed information on their origins and growth conditions. This work was supported by NIH grants CA075115 and CA104106 to D.T., Although it is generally accepted that cellular differentiation requires changes to transcriptional networks, dynamic regulation of promoters and enhancers at specific sets of genes has not been previously studied en masse. Exploiting the fact that active promoters and enhancers are transcribed, we simultaneously measured their activity in 19 human and 14 mouse time courses covering a wide range of cell types and biological stimuli. Enhancer RNAs, then messenger RNAs encoding transcription factors, dominated the earliest responses. Binding sites for key lineage transcription factors were simultaneously overrepresented in enhancers and promoters active in each cellular system. Our data support a highly generalizable model in which enhancer transcription is the earliest event in successive waves of transcriptional change during cellular differentiation or activation.