The proline isomerase Pin1 limits chromosome decondensation by stabilizing a histone’s association with chromatin, Raghuram et al. reveal.

Histone H1 incorporates into nucleosomes to enhance chromatin folding and condensation. Phosphorylation by the cyclin-dependent kinase Cdk2 promotes H1’s dissociation from chromatin, perhaps by altering the conformation of the histone’s C-terminal domain. Raghuram et al. were therefore interested in the observation that, by phosphorylating serine–proline motifs, Cdk2 generates potential binding sites for the enzyme Pin1, which can alter protein conformations by changing the configuration of proline residues.

Raghuram et al. found that Pin1 bound to phosphorylated H1 and promoted the histone’s dephosphorylation in vivo, probably by converting phosphoserine–proline bonds to the trans-configuration preferentially targeted by the phosphatase PP2A. In vitro experiments revealed that phosphorylation altered the conformation of nucleosome-associated H1 and that this was reversed by Pin1 binding. H1 was thus more stably associated with chromatin in cells expressing Pin1 compared with cells lacking the proline isomerase.

H1 is phosphorylated at transcriptionally active regions of the genome so that the surrounding chromatin relaxes enough to permit the transcriptional machinery access. Pin1 was also recruited to these regions, and, in the enzyme’s absence, they became more decondensed than usual as H1 phosphorylation levels increased and the histone’s association with chromatin was reduced.

Proline isomerization therefore counteracts H1 phosphorylation to prevent excessive decondensation during gene transcription. Senior author Michael Hendzel now wants to investigate Pin1’s effect on chromatin structure and gene expression in more detail.

et al
J. Cell Biol.

Author notes

Text by Ben Short