Condensin I folds theC. elegansgenome

Abstract

Structural Maintenance of Chromosomes (SMC) complexes, cohesin and condensins, were named for their roles in meiotic and mitotic chromosome separation and compaction. Recent data from mammalian cells and Drosophila have described additional roles for cohesin in folding the interphase genome into loops and domains. However, determinants of genome folding in holocentric species remain unclear. Using high-resolution chromosome conformation capture, we show that C. elegans chromosomes exhibit two types of compartments: a large-scale compartmentalization that corresponds to central vs telomere proximal regions and a small-scale compartmentalization that reflects epigenomic states. By systematically and acutely inactivating each SMC complex, we find that in contrast to other organisms, condensin I plays a major role in long-range genome folding, while cohesin creates small loops. Loss of condensin I causes genome-wide decompaction, chromosome mixing, and disappearance of TAD structures, while reinforcing fine-scale epigenomic compartments. Counter-intuitively, the removal of condensin I and its X-specific variant condensin IDC from the X chromosomes reveals the existence of a third compartment grouping together a subset of previously characterized loading sites for condensin IDC and binding sites for the X-targeting complex SDC. While transcriptional changes were minor for all autosomes upon cohesin, condensin II, and condensin I/IDC inactivation, removal of condensin I/IDC from the X chromosome led to transcriptional up-regulation of X-linked genes. In conclusion, we describe a novel function for C. elegans condensin I/IDC in holocentric interphase chromosome organization, which substitutes the role played by cohesin in other organisms.

Condensin DC loads and spreads from recruitment sites to create loop-anchored TADs inC. elegans

“…ln simulation, one-sided LEFs cannot form corner-peaks due to high frequency of gaps between two oppositely oriented LEFs [70]. This is unlikely to be a limitation in our system, because (i) in simulation, the corner-peaks can be ‘rescued’ with strong preferential loading at the boundary, and (ii) a recent preprint reported that the cleavage of DPY-26, a kleisin subunit shared by condensin l and DC, did not eliminate rex-rex corner-peaks [74]. Therefore, the corner-peak does not necessitate an explanation based on loop extrusion.…”

“…In mixed stage embryos and L3 worms we may be analyzing a maintenance/equilibrium state of X-chromosome organization. Hi-C data in a recent preprint presented that upon degradation of SDC-3 or cleavage of kleisin subunit DPY-26 TADs disappear but the rex-rex corner-peaks remain unperturbed [74]. This is in contrast to the genetic loss of SDC-2 resulting in the complete loss of all features of TADs [40, 55].…”

A layer cake model for plant and metazoan chromatin

“…Interestingly, facultative heterochromatin, which contains repressed genes, was at the time found together with euchromatin in the A compartment. This organisation in two compartments is conserved in multi-cellular eukaryotes, including plants [8] and species with holocentric chromosomes [7]. Principal features of chromatin compartmentalisation were later on shown to correlate with replication timing[24], TE content [5] and many other epigenetic marks [26].…”

Unique territorial and compartmental organization of chromosomes in the holocentric silkmoth

“…Aiming to explain pattern of contacts of S domains we turned to loop extrusion, a mechanism of chromosome organization seen across species, including holocentric nematodes 19,29 . In vertebrates, loop extrusion by the SMC complex cohesin, when occluded by extrusion boundaries, generates domains of local compaction, TADs.…”

“…Many Hi-C datasets have been generated to aid genome assembly [14][15][16][17][18] , but in-depth analyses of 3D genome organization have been performed only for model organisms, including mammals, flies, nematodes, yeasts, bacteria and plants [4][5][6][7][8][9][10][11][12][13][19][20][21][22] . A recent comparison of diverse organisms provided insights into differences in genome organization.…”