PT  - JOURNAL ARTICLE
AU  - Jessica B. Lee
AU  - Leandra M. Caywood
AU  - Jennifer Y. Lo
AU  - Nicholas Levering
AU  - Albert J. Keung
TI  - Mapping the dynamic transfer functions of epigenome editing
AID  - 10.1101/2021.01.05.425451
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.01.05.425451
4099  - http://biorxiv.org/content/early/2021/01/05/2021.01.05.425451.short
4100  - http://biorxiv.org/content/early/2021/01/05/2021.01.05.425451.full
AB  - Biological information can be encoded in the dynamics of signaling components which has been implicated in a broad range of physiological processes including stress response, oncogenesis, and stem cell differentiation. To study the complexity of information transfer across the eukaryotic promoter, we screened 119 dynamic conditions—modulating the frequency, intensity, and pulse width of light—regulating the binding of an epigenome editor to a fluorescent reporter. This system revealed highly tunable gene expression and filtering behaviors and provided the most comprehensive quantification to date of the maximum amount of information that can be reliably transferred across a promoter as ∼1.7 bits. Using a library of over 100 orthogonal epigenome editors, we further determined that chromatin state could be used to tune mutual information and expression levels, as well as completely alter the input-output transfer function of the promoter. This system unlocks the information-rich content of eukaryotic epigenome editing.Competing Interest StatementThe authors have declared no competing interest.