Danny Reinberg’s career-long investigation of the mechanistic basis of RNA polymerase II-mediated transcription in mammalian cells incorporated increasingly complex and biologically relevant contexts. The reconstitution of transcription initiation in vitro on naked DNA revealed fundamental mechanistic features of this process. The generation of biologically relevant chromatinized templates facilitated the discovery of FACT and its role in enabling the polymerase to traverse impeding nucleosomes.
A major effort was made towards understanding signals and factors that naturally convert the chromatin structure to a repressed state, inaccessible to the transcription machinery. The means by which repressive complexes (Sin3 and NuRD) foster transcriptionally inactive chromatin were revealed. Some of these processes are epigenetic, being both independent of DNA sequence and heritable such that distinct cellular gene expression programs are re-established in daughter cells. The laboratory investigated specific modifications of the histones that are associated with repressed chromatin with respect to their catalysis, their outcome to transcription and in some cases their inheritance. The mechanistic basis for how the epigenetically-related PRC2 complex establishes a repressive chromatin domain and how this domain is copied during cell division was derived. Investigations were initiated into epigenetic mechanisms within the context of a whole organism that exhibits social interaction: ants.