Fig 1.
SMC complexes form ring-like structures.
A cartoon of a cohesin (A) and condensin (B) protein complex shows the long coiled-coil SMC arms of the ring (blue; SMC1 and SMC3 for cohesin, SMC2 and SMC4 for condensin), as well as the subunits that interact at the head domains (N and C termini of RAD21 and SA for cohesin; Condensin-Associated Proteins CAPH2, CAPD3, and CAPG2 for condensin). In particular, the RAD21 and CAPH2 subunits (red, kleisin) are important for closing the ring at the SMC head domains. The interaction between the hinge domains of the SMC subunits of cohesin may serve as an entry gate for DNA into the ring, and the SMC3–RAD21 interface may serve as an exit gate. Cartoon adapted from [6]. SA, stromal antigen; SMC, structural maintenance of chromosome.
Fig 2.
Condensin II and TFIIIC binding co-occur at active gene clusters at TAD boundaries that interact to form compartments.
CAPH2, condensin-associated protein H2; TAD, topological associated domain; TFIIIC, Transcription Factor IIIC. An amalgam of data is shown for a region on mouse chromosome 8 (coordinates 58151693–122470100). In the Hi-C contact map [10], TADs are outlined in black. The insulation score, calculated in-house based on the method described in [24], helps to define TADs and boundary regions. Chromatin immunoprecipitation followed by deep sequencing (ChIP seq) data are shown for NCAPH2 [21], a subunit of condensin II, TFCIII90 subunit of TFIIIC [25], H3K4me3 [26], a marker of active promoters, and gene clusters. The blue arrows in the contact map indicate interactions between boundary domains, which are thought to form compartments.
Table 1.
SMC complexes, adaptor proteins, and associated histone modifications.
Fig 3.
Working models for how adaptor proteins and SMC complexes facilitate the formation of chromosomal domains by loop extrusion.
(A) A loop begins to form as DNA is extruded through the center of an SMC complex ring (blue). Protein rings may move along DNA until an adaptor protein (purple) is encountered that captures the SMC complex ring and halts the extrusion. (B) A region is depicted with cohesin and CTCF facilitating the formation of a topological domain by constraining the sequences at the base. CTCF sites tend to be arranged head-to-head [62]. A single cohesin ring may interact with CTCF and encircle two DNAs to form the base of the loop, which is the boundary between neighboring TADs. Alternatively, two cohesin rings may interact to facilitate the DNA–DNA interaction. (C) Multiple binding sites for condensin II and TFIIIC are found at TAD boundaries. It is not known whether a single condensin ring can encircle two DNAs; we have depicted one ring per DNA, similar to the handcuff model proposed for the bacterial SMC complex in loop extrusion. (D) Interactions between active genes at the base of multiple domains may facilitate the high levels of expression of housekeeping genes, perhaps via a local transcriptional hub (yellow). CTCF, CCCTC-binding factor; SMC, structural maintenance of chromosome; TAD, topological associated domain; TFIIIC, Transcription Factor IIIC.
Fig 4.
Proposed loop extrusion model for how the SMC complex in B. subtilis mediates the interaction between chromosome arms.
(A) Prior to condensin loading, ParB (purple) binds to a parS site. At this point, there is no interaction between chromosome arms. (B) The condensin complex (blue) loads at parS sites dependent on the ParB protein, and then “handcuffs” can move along DNA (black arrows), juxtaposing the two sides of the chromosome. (C) As more condensin loads at the parS site and spreads away from the site, and DNA replicates, the arms of the chromosomes are zipped up. Given the structural similarities between SMC complexes from bacteria and eukaryotes, it seems likely there will be common themes by which SMC complexes organize DNA. Cartoon adapted from [65]. ParB, Partition B; SMC, structural maintenance of chromosome.