Kinetic proofreading of gene activation by chromatin remodeling

Abstract

Gene activation in eukaryotes involves the concerted action of histone tail modifiers, chromatin remodelers, and transcription factors, whose precise coordination is currently unknown. We demonstrate that the experimentally observed interactions of the molecules are in accord with a kinetic proofreading scheme. Our finding could provide a basis for the development of quantitative models for gene regulation in eukaryotes based on the combinatorical interactions of chromatin modifiers.

Figure 1. The sequence of regulatory events supposed in our model (schematic).

Top: nucleosome with one histone tail carrying amino acid modifications. Middle: recruitment of a remodeling complex (R) with a histone modifier recognition unit (dark green) and the ATP-active domain (red). The DNA is partially loosened from the histone octamer. Bottom: recruitment of a transcription factor (T).

Figure 2. Kinetic proofreading scheme for the regulation of transcription initiation in chromatin.