Somatic structural variant formation is guided by and influences genome architecture
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Somatic structural variant formation is guided by and influences genome architecture. / Sidiropoulos, Nikos; Mardin, Balca R; Rodríguez-González, F. Germán; Bochkov, Ivan D.; Garg, Shilpa; Stuetz, Adrian M; Korbel, Jan O.; Aiden, Erez Lieberman; Weischenfeldt, Joachim.
In: Genome Research, Vol. 32, No. 4, 2022, p. 643-655.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Somatic structural variant formation is guided by and influences genome architecture
AU - Sidiropoulos, Nikos
AU - Mardin, Balca R
AU - Rodríguez-González, F. Germán
AU - Bochkov, Ivan D.
AU - Garg, Shilpa
AU - Stuetz, Adrian M
AU - Korbel, Jan O.
AU - Aiden, Erez Lieberman
AU - Weischenfeldt, Joachim
N1 - Published by Cold Spring Harbor Laboratory Press.
PY - 2022
Y1 - 2022
N2 - The occurrence and formation of genomic structural variants (SV) is known to be influenced by the 3D chromatin architecture, but the extent and magnitude have been challenging to study. Here, we apply Hi-C to study chromatin organization before and after induction of chromothripsis in human cells. We use Hi-C to manually assemble the derivative chromosomes following the occurrence of massive complex rearrangements, which allowed us to study the sources of SV formation and their consequences on gene regulation. We observe an action-reaction interplay whereby the 3D chromatin architecture directly impacts the location and formation of SVs. In turn, the SVs reshape the chromatin organization to alter the local topologies, replication timing, and gene regulation in cis We show that SVs have a strong tendency to occur between similar chromatin compartments and replication timing regions. Moreover, we find that SVs frequently occur at 3D loop-anchors, that SVs can cause a switch in chromatin compartments and replication timing, and that this is a major source of SV-mediated effects on nearby gene expression changes. Finally, we provide evidence for a general mechanistic bias of the 3D chromatin on SV occurrence using data from more than 2,700 patient-derived cancer genomes.
AB - The occurrence and formation of genomic structural variants (SV) is known to be influenced by the 3D chromatin architecture, but the extent and magnitude have been challenging to study. Here, we apply Hi-C to study chromatin organization before and after induction of chromothripsis in human cells. We use Hi-C to manually assemble the derivative chromosomes following the occurrence of massive complex rearrangements, which allowed us to study the sources of SV formation and their consequences on gene regulation. We observe an action-reaction interplay whereby the 3D chromatin architecture directly impacts the location and formation of SVs. In turn, the SVs reshape the chromatin organization to alter the local topologies, replication timing, and gene regulation in cis We show that SVs have a strong tendency to occur between similar chromatin compartments and replication timing regions. Moreover, we find that SVs frequently occur at 3D loop-anchors, that SVs can cause a switch in chromatin compartments and replication timing, and that this is a major source of SV-mediated effects on nearby gene expression changes. Finally, we provide evidence for a general mechanistic bias of the 3D chromatin on SV occurrence using data from more than 2,700 patient-derived cancer genomes.
U2 - 10.1101/gr.275790.121
DO - 10.1101/gr.275790.121
M3 - Journal article
C2 - 35177558
VL - 32
SP - 643
EP - 655
JO - Genome Research
JF - Genome Research
SN - 1088-9051
IS - 4
ER -
ID: 298648895