A dynamic structural unit of phase-separated heterochromatin protein 1α as revealed by integrative structural analyses.

The heterochromatin protein HP1α consists of an N-terminal disordered tail (N-tail), chromodomain (CD), hinge region (HR), and C-terminal chromo shadow domain (CSD). While CD binds to the lysine9-trimethylated histone H3 (H3K9me3) tail in nucleosomes, CSD forms a dimer bridging two nucleosomes with H3K9me3. Phosphorylation of serine residues in the N-tail enhances both H3K9me3 binding and liquid-liquid phase separation (LLPS) by HP1α.

Characterization of the Swi6/HP1 binding motif in its partner protein reveals the basis for the functional divergence of the HP1 family proteins in fission yeast.

The heterochromatin protein 1 (HP1) family recognizes lysine 9-methylated histone H3 (H3K9me) and recruits other transacting factors to establish higher order chromatin structures. In the fission yeast Schizosaccharomyces pombe (S. pombe), two HP1 family proteins, Swi6 and Chp2, play distinct roles in recruiting transacting factors: Swi6 primarily recruits Epe1, a Jumonji C domain-containing protein involved in histone H3K9 demethylation, whereas Chp2 recruits Mit1, a component of the Snf2/Hdac Repressive Complex.

Cooperative DNA-binding activities of Chp2 are critical for its function in heterochromatin assembly.

Heterochromatin protein 1 (HP1) is an evolutionarily conserved protein that plays a critical role in heterochromatin assembly. HP1 proteins share a basic structure consisting of an N-terminal chromodomain (CD) and a C-terminal chromoshadow domain (CSD) linked by a disordered hinge region. The CD recognizes histone H3 lysine 9 methylation, a hallmark of heterochromatin, while the CSD forms a dimer to recruit other chromosomal proteins.

Structural basis for histone variant H3tK27me3 recognition by PHF1 and PHF19.

The Polycomb repressive complex 2 (PRC2) is a multicomponent histone H3K27 methyltransferase complex, best known for silencing the genes during embryonic development. The Polycomb-like proteins PHF1, MTF2, and PHF19 are critical components of PRC2 by stimulating its catalytic activity in embryonic stem cells. The Tudor domains of PHF1/19 have been previously shown to be readers of H3K36me3 in vitro.

H3K14 ubiquitylation promotes H3K9 methylation for heterochromatin assembly.

The methylation of histone H3 at lysine 9 (H3K9me), performed by the methyltransferase Clr4/SUV39H, is a key event in heterochromatin assembly. In fission yeast, Clr4, together with the ubiquitin E3 ligase Cul4, forms the Clr4 methyltransferase complex (CLRC), whose physiological targets and biological role are currently unclear. Here, we show that CLRC-dependent H3 ubiquitylation regulates Clr4's methyltransferase activity.

Mitotic phosphorylation of HP1α regulates its cell cycle-dependent chromatin binding.

Heterochromatin protein 1 (HP1) is an evolutionarily conserved chromosomal protein that plays a crucial role in heterochromatin-mediated gene silencing. We previously showed that mammalian HP1α is constitutively phosphorylated at its N-terminal serine residues by casein kinase II (CK2), and that this phosphorylation enhances HP1α's binding specificity for nucleosomes containing lysine 9-methylated histone H3 (H3K9me). Although the presence of additional HP1α phosphorylation during mitosis was reported more than a decade ago, its biological significance remains largely elusive.