Regulation of Centromeric Heterochromatin in the Cell Cycle by Phosphorylation of Histone H3 Tyrosine 41

Constitutive heterochromatin packages long stretches of repetitive DNA sequences at the centromere and telomere, and ensures genomic integrity at these loci by preventing aberrant recombination and transcription. The chromatin scaffold of heterochromatin is dynamically regulated in the cell cycle, and inheritance of the epigenetically silenced state is dependent on a transcriptional event imposed on the underlying non-coding RNA in conjunction with the DNA replicative phase. Heterochromatin becomes transiently loosened in response to a reduction in the binding of Swi6, a heterochromatin protein, and this allows RNA polymerase II access to the underlying sequence. The derived transcripts, in turn, drive heterochromatin formation via the recruitment of other silencing factors. It remains unclear how heterochromatin becomes decompacted in a cell cycle-specific manner. Here, we describe a mechanism of heterochromatin decompaction initiated by a novel histone modification, histone H3 tyrosine 41 phosphorylation (H3Y41p). We will discuss how H3Y41p cooperates with other regulatory pathways to enforce cell cycle-dependent regulation of constitutive heterochromatin.