A transcription factor pulse can prime chromatin for heritable transcriptional memory

Iberg-Badeaux A. et al.

Short-term and long-term transcriptional memory is the phenomenon whereby the kinetics or magnitude of gene induction is enhanced following a prior induction period. Short-term memory persists within one cell generation or in post-mitotic cells, while long-term memory can survive multiple rounds of cell division. We have developed a tissue culture model to study the epigenetic basis for long-term transcriptional memory (LTTM), and subsequently used this model to better understand the epigenetic mechanisms that enable heritable memory of temporary stimuli. We find that a pulse of transcription factor C/EBPα induces LTTM on a subset of target genes that survives 9 cell divisions. The chromatin landscape at genes that acquire LTTM is more repressed as compared to those genes that do not exhibit memory, akin to a latent state. We show through ChIP and chemical inhibitor studies that Pol II elongation is important for establishing memory in this model, but that Pol II itself is not retained as part of the memory mechanism. More generally, our work reveals that a transcription factor involved in lineage specification can induce LTTM, and that failure to re-repress chromatin is one epigenetic mechanism underlying transcriptional memory.


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December, 2016


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