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X Chromosome Domain Architecture Regulates Caenorhabditis elegans Lifespan but Not Dosage Compensation.
Dev Cell. 2019 10 21; 51(2):192-207.e6.DC

Abstract

Mechanisms establishing higher-order chromosome structures and their roles in gene regulation are elusive. We analyzed chromosome architecture during nematode X chromosome dosage compensation, which represses transcription via a dosage-compensation condensin complex (DCC) that binds hermaphrodite Xs and establishes megabase-sized topologically associating domains (TADs). We show that DCC binding at high-occupancy sites (rex sites) defines eight TAD boundaries. Single rex deletions disrupted boundaries, and single insertions created new boundaries, demonstrating that a rex site is necessary and sufficient to define DCC-dependent boundary locations. Deleting eight rex sites (8rexΔ) recapitulated TAD structure of DCC mutants, permitting analysis when chromosome-wide domain architecture was disrupted but most DCC binding remained. 8rexΔ animals exhibited no changes in X expression and lacked dosage-compensation mutant phenotypes. Hence, TAD boundaries are neither the cause nor the consequence of DCC-mediated gene repression. Abrogating TAD structure did, however, reduce thermotolerance, accelerate aging, and shorten lifespan, implicating chromosome architecture in stress responses and aging.

Authors+Show Affiliations

Howard Hughes Medical Institute and Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.Howard Hughes Medical Institute and Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.Howard Hughes Medical Institute and Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.Howard Hughes Medical Institute and Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.Howard Hughes Medical Institute and Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.Calico Life Sciences, South San Francisco, CA 94080, USA.Howard Hughes Medical Institute and Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.Calico Life Sciences, South San Francisco, CA 94080, USA.Howard Hughes Medical Institute and Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.Howard Hughes Medical Institute and Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA. Electronic address: bjmeyer@berkeley.edu.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

31495695

Citation

Anderson, Erika C., et al. "X Chromosome Domain Architecture Regulates Caenorhabditis Elegans Lifespan but Not Dosage Compensation." Developmental Cell, vol. 51, no. 2, 2019, pp. 192-207.e6.
Anderson EC, Frankino PA, Higuchi-Sanabria R, et al. X Chromosome Domain Architecture Regulates Caenorhabditis elegans Lifespan but Not Dosage Compensation. Dev Cell. 2019;51(2):192-207.e6.
Anderson, E. C., Frankino, P. A., Higuchi-Sanabria, R., Yang, Q., Bian, Q., Podshivalova, K., Shin, A., Kenyon, C., Dillin, A., & Meyer, B. J. (2019). X Chromosome Domain Architecture Regulates Caenorhabditis elegans Lifespan but Not Dosage Compensation. Developmental Cell, 51(2), 192-e6. https://doi.org/10.1016/j.devcel.2019.08.004
Anderson EC, et al. X Chromosome Domain Architecture Regulates Caenorhabditis Elegans Lifespan but Not Dosage Compensation. Dev Cell. 2019 10 21;51(2):192-207.e6. PubMed PMID: 31495695.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - X Chromosome Domain Architecture Regulates Caenorhabditis elegans Lifespan but Not Dosage Compensation. AU - Anderson,Erika C, AU - Frankino,Phillip A, AU - Higuchi-Sanabria,Ryo, AU - Yang,Qiming, AU - Bian,Qian, AU - Podshivalova,Katie, AU - Shin,Aram, AU - Kenyon,Cynthia, AU - Dillin,Andrew, AU - Meyer,Barbara J, Y1 - 2019/09/05/ PY - 2019/03/26/received PY - 2019/06/26/revised PY - 2019/08/06/accepted PY - 2019/9/10/pubmed PY - 2020/5/28/medline PY - 2019/9/10/entrez KW - X chromosome dosage compensation KW - aging KW - condensin KW - gene expression KW - higher-order chromosome structure KW - lifespan KW - proteotoxic stress KW - topologically associating domains SP - 192 EP - 207.e6 JF - Developmental cell JO - Dev Cell VL - 51 IS - 2 N2 - Mechanisms establishing higher-order chromosome structures and their roles in gene regulation are elusive. We analyzed chromosome architecture during nematode X chromosome dosage compensation, which represses transcription via a dosage-compensation condensin complex (DCC) that binds hermaphrodite Xs and establishes megabase-sized topologically associating domains (TADs). We show that DCC binding at high-occupancy sites (rex sites) defines eight TAD boundaries. Single rex deletions disrupted boundaries, and single insertions created new boundaries, demonstrating that a rex site is necessary and sufficient to define DCC-dependent boundary locations. Deleting eight rex sites (8rexΔ) recapitulated TAD structure of DCC mutants, permitting analysis when chromosome-wide domain architecture was disrupted but most DCC binding remained. 8rexΔ animals exhibited no changes in X expression and lacked dosage-compensation mutant phenotypes. Hence, TAD boundaries are neither the cause nor the consequence of DCC-mediated gene repression. Abrogating TAD structure did, however, reduce thermotolerance, accelerate aging, and shorten lifespan, implicating chromosome architecture in stress responses and aging. SN - 1878-1551 UR - https://www.unboundmedicine.com/medline/citation/31495695/X_Chromosome_Domain_Architecture_Regulates_Caenorhabditis_elegans_Lifespan_but_Not_Dosage_Compensation_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1534-5807(19)30664-1 DB - PRIME DP - Unbound Medicine ER -