The intrinsically disordered tail of ESCO1 binds DNA in a charge-dependent manner.

ESCO1 is an acetyltransferase enzyme that regulates chromosome organization and gene expression. It does this by modifying the Smc3 subunit of the Cohesin complex. Although ESCO1 is enriched at the base of chromatin loops in a Cohesin-dependent manner, precisely how it interacts with chromatin is unknown. Here we show that the basic and intrinsically disordered tail of ESCO1 binds DNA with very high affinity, likely through electrostatic interaction. We show that neutralization of positive residues in the N-tail reduces both DNA binding in vitro and association of the enzyme with chromatin in cells. Additionally, disruption of the chromatin state and charge distribution reduces chromatin bound ESCO1. Strikingly, defects in DNA binding do not affect total SMC3 acetylation or sister chromatid cohesion, suggesting that ESCO1-dependent acetylation can occur independently of direct chromatin association. We conclude that the intrinsically disordered tail of ESCO1 binds DNA with both high affinity and turnover, but surprisingly, ESCO1 catalytic activity occurs independently of direct DNA binding by the enzyme.