Centromeres of eukaryotes are frequently associated with constitutive 
heterochromatin and their activity appears to be coregulated by epigenetic 
modification of higher order chromatin. Recently, we isolated murine (Suv39h1) 
and human (SUV39H1) homologues of the dominant Drosophila suppressor of position 
effect variegation Su(var)3-9, which is also related to the S. pombe silencing 
factor Clr4. We have shown that mammalian Su(var)3-9 homologues encode novel 
centromeric proteins on metaphase-arrested chromosomes. Here, we describe a 
detailed analysis of the chromatin distribution of human SUV39H1 during the cell 
cycle. Although there is significant heterochromatic overlap between SUV39H1 and 
M31 (HP1(beta)) during interphase, mitotic SUV39H1 displays a more restricted 
spatial and temporal association pattern with metaphase chromosomes than M31 
(HP1(beta)), or the related HP1(&agr;) gene product. SUV39H1 specifically 
accumulates at the centromere during prometaphase but dissociates from 
centromeric positions at the meta- to anaphase transition. In addition, SUV39H1 
selectively associates with the active centromere of a dicentric chromosome and 
also with a neocentromere. Interestingly, SUV39H1 is shown to be a 
phosphoprotein with modifications at serine and, to a lesser degree, also at 
threonine residues. Whereas SUV39H1 steady-state protein levels appear constant 
during the cell cycle, two additional phosphorylated isoforms are detected in 
mitotic extracts. This intriguing localisation and modification pattern would be 
consistent with a regulatory role(s) for SUV39H1 in participating in higher 
order chromatin organisation at mammalian centromeres.