TY - JOUR
T1 - Genome folding principles uncovered in condensin-depleted mitotic chromosomes
AU - Zhao, Han
AU - Lin, Yinzhi
AU - Lin, En
AU - Liu, Fuhai
AU - Shu, Lirong
AU - Jing, Dannan
AU - Wang, Baiyue
AU - Wang, Manzhu
AU - Shan, Fengnian
AU - Zhang, Lin
AU - Lam, Jessica C.
AU - Midla, Susannah C.
AU - Giardine, Belinda M.
AU - Keller, Cheryl A.
AU - Hardison, Ross C.
AU - Blobel, Gerd A.
AU - Zhang, Haoyue
N1 - Publisher Copyright:
© The Author(s), under exclusive licence to Springer Nature America, Inc. 2024.
PY - 2024/6
Y1 - 2024/6
N2 - During mitosis, condensin activity is thought to interfere with interphase chromatin structures. To investigate genome folding principles in the absence of chromatin loop extrusion, we codepleted condensin I and condensin II, which triggered mitotic chromosome compartmentalization in ways similar to that in interphase. However, two distinct euchromatic compartments, indistinguishable in interphase, emerged upon condensin loss with different interaction preferences and dependencies on H3K27ac. Constitutive heterochromatin gradually self-aggregated and cocompartmentalized with facultative heterochromatin, contrasting with their separation during interphase. Notably, some cis-regulatory element contacts became apparent even in the absence of CTCF/cohesin-mediated structures. Heterochromatin protein 1 (HP1) proteins, which are thought to partition constitutive heterochromatin, were absent from mitotic chromosomes, suggesting, surprisingly, that constitutive heterochromatin can self-aggregate without HP1. Indeed, in cells traversing from M to G1 phase in the combined absence of HP1α, HP1β and HP1γ, constitutive heterochromatin compartments are normally re-established. In sum, condensin-deficient mitotic chromosomes illuminate forces of genome compartmentalization not identified in interphase cells.
AB - During mitosis, condensin activity is thought to interfere with interphase chromatin structures. To investigate genome folding principles in the absence of chromatin loop extrusion, we codepleted condensin I and condensin II, which triggered mitotic chromosome compartmentalization in ways similar to that in interphase. However, two distinct euchromatic compartments, indistinguishable in interphase, emerged upon condensin loss with different interaction preferences and dependencies on H3K27ac. Constitutive heterochromatin gradually self-aggregated and cocompartmentalized with facultative heterochromatin, contrasting with their separation during interphase. Notably, some cis-regulatory element contacts became apparent even in the absence of CTCF/cohesin-mediated structures. Heterochromatin protein 1 (HP1) proteins, which are thought to partition constitutive heterochromatin, were absent from mitotic chromosomes, suggesting, surprisingly, that constitutive heterochromatin can self-aggregate without HP1. Indeed, in cells traversing from M to G1 phase in the combined absence of HP1α, HP1β and HP1γ, constitutive heterochromatin compartments are normally re-established. In sum, condensin-deficient mitotic chromosomes illuminate forces of genome compartmentalization not identified in interphase cells.
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U2 - 10.1038/s41588-024-01759-x
DO - 10.1038/s41588-024-01759-x
M3 - Article
C2 - 38802567
AN - SCOPUS:85194563940
SN - 1061-4036
VL - 56
SP - 1213
EP - 1224
JO - Nature Genetics
JF - Nature Genetics
IS - 6
ER -