A bromodomain protein, MCAP, associates with mitotic chromosomes and effects, G(2)-to-M transition

We describe a novel nuclear factor called mitotic chromosome-associated pro tein (MCAP), which belongs to the poorly understood BET subgroup of the bro modomain superfamily. Expression of the 200-kDa MCAP was linked to cell div ision, as it was induced by growth stimulation and repressed by growth inhi bition. The most notable feature of MCAP was its association with chromosom es during mitosis, observed at a time when the majority of nuclear regulato ry factors were released into the cytoplasm, coinciding with global cessati on of transcription. Indicative of its predominant interaction with euchrom atin, MCAP localized on mitotic chromosomes with exquisite specificity: (i) MCAP-chromosome association became evident subsequent to the initiation of histone H3 phosphorylation and early chromosomal condensation; and (ii) MC AP was absent from centromeres, the sites of heterochromatin. Supporting a role for MCAP in G(2)/M transition, microinjection of anti-MCAP antibody in to HeLa cell nuclei completely inhibited the entry into mitosis, without ab rogating the ongoing DNA replication. These results suggest that MCAP plays a role in a process governing chromosomal dynamics during mitosis.