Regulation of transcription by H1 phosphorylation in Tetrahymena is position independent and requires clustered sites

In Tetrahymena cells, constitutive phosphorylation of histone H1 phenocopies the loss of Hi from chromatin. Regulation of transcription by Hi phosphorylation is achieved by altering the overall charges of a small domain. Here, we further explore the electrostatic properties of this domain and the mechanism by which it regulates transcription. We demonstrate that the regulatory effect of the clustered charges does not require any long-range interaction and is position independent. However, when the same number of charges was dispersed throughout the H1 molecule, the effect became undetectable. The results are explained by a nucleation-propagation model and provide in vivo evidence that the synergy of the clustered positive charges plays a role in histone function and gene regulation.