Mechanism of Long-Range Chromosome Motion Triggered by Gene Activation

Movement of chromosome sites within interphase cells is critical for numerous pathways including RNA transcription and genome organization. Yet, a mechanism for reorganizing chromatin in response to these events had not been reported. Here, we delineate a molecular chaperone-dependent pathway for relocating activated gene loci in yeast. Our presented data support a model in which a two-authentication system mobilizes a gene promoter through a dynamic network of polymeric nuclear actin. Transcription factor-dependent nucleation of a myosin motor propels the gene locus through the actin matrix, and fidelity of the actin association was ensured by ARP-containing chromatin remodelers. Motor activity of nuclear myosin was dependent on the Hsp90 chaperone. Hsp90 further contributed by biasing the remodeler-actin interaction toward nucleosomes with the non-canonical histone H2A.Z, thereby focusing the pathway on select sites such as transcriptionally active genes. Together, the system provides a rapid and effective means to broadly yet selectively mobilize chromatin sites. [Display omitted] •Chromatin motion is dependent upon nuclear chaperones, remodelers, myosin, and actin•Allosterically regulated transcription factors nucleate myosin to select chromatin loci•Motor activity of nuclear myosin relies on molecular chaperones•ARP-containing remodelers act as chromatin transport processivity factors Chromosome reorganization is a central process critical for development and to maintain normal cell homeostasis. Here, Wang et al. report on a pathway able to direct the select movement of chromatin loci in interphase cells using the concerted activities of nuclear molecular chaperones, actin, myosin, and chromatin remodelers.