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X Chromosome Domain Architecture Regulates Caenorhabditis elegans Lifespan but Not Dosage Compensation.


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 (8rex?) recapitulated TAD structure of DCC mutants, permitting analysis when chromosome-wide domain architecture was disrupted but most DCC binding remained. 8rex? 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.

SUBMITTER: Anderson EC 

PROVIDER: S-EPMC6810858 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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X Chromosome Domain Architecture Regulates Caenorhabditis elegans Lifespan but Not Dosage Compensation.

Anderson Erika C EC   Frankino Phillip A PA   Higuchi-Sanabria Ryo R   Yang Qiming Q   Bian Qian Q   Podshivalova Katie K   Shin Aram A   Kenyon Cynthia C   Dillin Andrew A   Meyer Barbara J BJ  

Developmental cell 20190905 2


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 boun  ...[more]

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