TY - JOUR
T1 - Chromosome compartmentalization alterations in prostate cancer cell lines model disease progression
AU - Martin, Rebeca San
AU - Das, Priyojit
AU - Marques, Renata Dos Reis
AU - Xu, Yang
AU - Roberts, Justin M.
AU - Sanders, Jacob T.
AU - Golloshi, Rosela
AU - McCord, Rachel Patton
N1 - Publisher Copyright:
© 2021 San Martin et al.
PY - 2022/2/7
Y1 - 2022/2/7
N2 - Prostate cancer aggressiveness and metastatic potential are influenced by gene expression and genomic aberrations, features that can be influenced by the 3D structure of chromosomes inside the nucleus. Using chromosome conformation capture (Hi-C), we conducted a systematic genome architecture comparison on a cohort of cell lines that model prostate cancer progression, from normal epithelium to bone metastasis. We describe spatial compartment identity (A-open versus B-closed) changes with progression in these cell lines and their relation to gene expression changes in both cell lines and patient samples. In particular, 48 gene clusters switch from the B to the A compartment, including androgen receptor, WNT5A,andCDK14. These switches are accompanied by changes in the structure, size, and boundaries of topologically associating domains (TADs). Further, compartment changes in chromosome 21 are exacerbated with progression and may explain, in part, the genesis of the TMPRSS2-ERG translocation. These results suggest that discrete 3D genome structure changes play a deleterious role in prostate cancer progression.
AB - Prostate cancer aggressiveness and metastatic potential are influenced by gene expression and genomic aberrations, features that can be influenced by the 3D structure of chromosomes inside the nucleus. Using chromosome conformation capture (Hi-C), we conducted a systematic genome architecture comparison on a cohort of cell lines that model prostate cancer progression, from normal epithelium to bone metastasis. We describe spatial compartment identity (A-open versus B-closed) changes with progression in these cell lines and their relation to gene expression changes in both cell lines and patient samples. In particular, 48 gene clusters switch from the B to the A compartment, including androgen receptor, WNT5A,andCDK14. These switches are accompanied by changes in the structure, size, and boundaries of topologically associating domains (TADs). Further, compartment changes in chromosome 21 are exacerbated with progression and may explain, in part, the genesis of the TMPRSS2-ERG translocation. These results suggest that discrete 3D genome structure changes play a deleterious role in prostate cancer progression.
KW - Cancer
KW - Chromatin or epigenetics
KW - Systems and Computational Biology
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UR - http://www.scopus.com/inward/citedby.url?scp=85122516867&partnerID=8YFLogxK
U2 - 10.1083/jcb.202104108
DO - 10.1083/jcb.202104108
M3 - Article
C2 - 34889941
AN - SCOPUS:85122516867
SN - 0021-9525
VL - 221
JO - Journal of Cell Biology
JF - Journal of Cell Biology
IS - 2
M1 - e202104108
ER -