Proposed mechanisms for the roles of three histone variants. (a) The H3.3 variant is remodeled into octamers at sites of active transcription, where it helps stabilize chromatin in an open, transcriptionally active form. (b) The CENPA variant is localized to the centromere region; it contains a unique extension that may help attach the chromosome to the kinetochore. (c) H2AX localizes to sites of double-strand breaks, where it becomes phosphorylated on Ser¹³⁹ and attracts DNA repair complexes to the site.