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. 2022 Jan 6;220(2):iyab197. doi: 10.1093/genetics/iyab197

Figure 6.

Figure 6

Targeting the dosage compensation complex to X chromosomes. (A) The DCC contains 10 identified subunits, including five condensin-like subunits (DPY-27, MIX-1, DPY-26, DPY-28, and CAPG-1) that are homologous to canonical condensin subunits SMC2, SMC4, CAP-H, CAP-D2, and CAP-G1, respectively, which are conserved from yeast to human. The DCC also includes the XX-specific novel protein SDC-2 that is expressed specifically in XX animals and triggers assembly of the DCC onto X. Two DCC subunits aid SDC-2 in recruiting the complex to X: SDC-3 (a zinc-finger protein) and DPY-30 (also a subunit of the MLL/COMPASS H3K4me3 methyltransferase complex). Two additional subunits, SDC-1 (a zinc-finger protein) and DPY-21 (Jumonji C H4K20me2 demethylase), are required for DCC activity but not for assembly of the DCC onto X. (B) Possible models for the mechanism by which the DCC is targeted to X. A single site on X could recruit the DCC and nucleate spreading across X (1). A limited number of sites could recruit the DCC and either nucleate DCC spreading (arrows) (2) or not (3). If no spreading occurs, the DCC would act over long distance to repress gene expression (3). A high density of sites could recruit the DCC but no spreading would occur, implying direct, short-range gene regulation by the DCC (4). Model 2 representing DCC recruitment to specific sites on X followed by spreading is the mechanism supported by all available data. (C) Enlargement of the DNA section from the 4.37- to 4.40-Mb region on the left end of X showing adjacent rex and dox DCC binding sites mapped by ChIP-chip (shown) and ChIP-seq experiments and assayed for autonomous DCC recruitment ability in vivo. Sites were classified into two categories based on their ability to bind the complex when detached from X chromosomes. rex sites (recruitment elements on X) bind the complex robustly in vivo when they are detached from X and are present either in multiple copies on extrachromosomal arrays or in low copy number integrated onto an autosome. dox sites (dependent on X) fail to bind the DCC when detached from X and require the X-chromosome context of rex sites for their DCC binding ability. DCC binding at rex sites facilitates binding at dox sites nearby, but the mechanism of spreading is not known. (D) A 12 base pair consensus motif identified by motif searches is enriched at rex sites relative to dox sites and on X chromosomes relative to autosomes. It recruits the DCC to X but cannot be the sole X-enriched motif to do so. Mutations within the motif disrupt the ability of rex sites to bind the DCC. (E) DCC binding to chromosome V is facilitated by proximity to rex sites located on the X part of an X:V fusion chromosome. DCC binding on X is able to spread into the 2 Mb region of chromosome V adjacent to the fusion break point. Chromosomes X (17.7 Mb) and V (20.9 Mb) are drawn to scale.