PT  - JOURNAL ARTICLE
AU  - Mike V. Van
AU  - Taihei Fujimori
AU  - Lacramioara Bintu
TI  - Nanobody-mediated control of gene expression and epigenetic memory
AID  - 10.1101/2020.09.09.290015
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.09.09.290015
4099  - http://biorxiv.org/content/early/2020/09/10/2020.09.09.290015.short
4100  - http://biorxiv.org/content/early/2020/09/10/2020.09.09.290015.full
AB  - Targeting chromatin regulators to specific genomic locations for gene control is emerging as a powerful method in basic research and synthetic biology. However, many chromatin regulators are large, making them difficult to deliver and combine in mammalian cells. Here, we developed a new strategy for gene control using small nanobodies that bind and recruit endogenous chromatin regulators to a gene. We show that an antiGFP nanobody can be used to simultaneously visualize GFP-tagged chromatin regulators and control gene expression, and that nanobodies against HP1 and DNMT1 can silence a reporter gene. Moreover, combining nanobodies together or with other regulators, such as DNMT3A or KRAB, can enhance silencing speed and epigenetic memory. Finally, we use the slow silencing speed and high memory of antiDNMT1 to build a signal duration timer and recorder. These results set the basis for using nanobodies against chromatin regulators for controlling gene expression and epigenetic memory.Competing Interest StatementThe authors have declared no competing interest.