Resolving the mechanisms of gene regulation by SMC protein complexes
Biochemistry
Structural Biology
Cell Biology
Final Report Abstract
Dosage compensation mechanisms ensure balanced gene expression across sexes with differing numbers of X chromosomes. In Caenorhabditis elegans, this balance is maintained by the Dosage Compensation Complex (DCC), which comprises a specialized Structural Maintenance of Chromosomes (SMC) complex known as condensin IDC, along with Sex Determination of Dosage Compensation (SDC) proteins. We present evidence that SDC proteins form phase-separated condensates both in vivo and in vitro. Our findings highlight the critical role of a large intrinsically disordered region containing positively charged patches in one of the SDC proteins, which is essential for condensate formation and dosage compensation. In addition, we delineate the interaction interface between SDC proteins and condensin IDC and elucidate its structure using cryo-electron microscopy. We further show that condensin IDC actively extrudes DNA loops, exhibiting characteristics akin to other SMC protein complexes, and resolve the catalytic core of its DNA motor to near-atomic resolution. Based on these results, we propose a model that attributes a novel function to SMC-mediated DNA loop extrusion, enabling chromosome-wide regulation of gene expression.
