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

Developmental cell (2019-09-10)
Erika C Anderson, Phillip A Frankino, Ryo Higuchi-Sanabria, Qiming Yang, Qian Bian, Katie Podshivalova, Aram Shin, Cynthia Kenyon, Andrew Dillin, Barbara J Meyer
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Methyl viologen dichloride hydrate, 98%
Supelco
Paraquat dichloride hydrate, PESTANAL®, analytical standard