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

Developmental cell | 2019

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.

Pubmed ID: 31495695 RIS Download

Associated grants

  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM030702
  • Agency: NIGMS NIH HHS, United States
    Id: T32 GM007232
  • Agency: NIA NIH HHS, United States
    Id: F32 AG053023
  • Agency: NIGMS NIH HHS, United States
    Id: R35 GM131845
  • Agency: NIH HHS, United States
    Id: S10 OD018174
  • Agency: Howard Hughes Medical Institute, United States

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This is a list of tools and resources that we have found mentioned in this publication.


ChIP-seq (tool)

RRID:SCR_001237

Set of software modules for performing common ChIP-seq data analysis tasks across the whole genome, including positional correlation analysis, peak detection, and genome partitioning into signal-rich and signal-poor regions. The tools are designed to be simple, fast and highly modular. Each program carries out a well defined data processing procedure that can potentially fit into a pipeline framework. ChIP-Seq is also freely available on a Web interface.

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SAMTOOLS (tool)

RRID:SCR_002105

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TopHat (tool)

RRID:SCR_013035

Software tool for fast and high throughput alignment of shotgun cDNA sequencing reads generated by transcriptomics technologies. Fast splice junction mapper for RNA-Seq reads. Aligns RNA-Seq reads to mammalian-sized genomes using ultra high-throughput short read aligner Bowtie, and then analyzes mapping results to identify splice junctions between exons.TopHat2 is accurate alignment of transcriptomes in presence of insertions, deletions and gene fusions.

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CummeRbund (tool)

RRID:SCR_014568

Software R package used for simplifying and analyzing Cufflink RNA-Seq output. This program takes various output files from a cuffdiff run and creates a SQLite database of the results that will describe the appropriate relationships between the genes, transcripts, transcription start sites and CDS regions.

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Cufflinks (tool)

RRID:SCR_014597

Software tool for transcriptome assembly and differential expression analysis for RNA-Seq. Includes script called cuffmerge that can be used to merge together several Cufflinks assemblies. It also handles running Cuffcompare as well as automatically filtering a number of transfrags that are likely to be artifacts. If the researcher has a reference GTF file, the researcher can provide it to the script to more effectively merge novel isoforms and maximize overall assembly quality.

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Bowtie 2 (tool)

RRID:SCR_016368

Ultrafast and memory efficient tool for aligning sequencing reads to long reference sequences. Supports gapped, local, and paired end alignment modes. More suited to finding longer, gapped alignments in comparison with original Bowtie method.

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Deeptools (tool)

RRID:SCR_016366

Python based tools to process, visualize and analyse high-throughput sequencing data, such as ChIP-seq, RNA-seq or MNase-seq. Implemented within Galaxy framework. Used to perform complete bioinformatic workflows ranging from quality controls and normalizations of aligned reads to integrative analyses, including clustering and visualization approaches.

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AffiniPure Rabbit Anti-Rat IgG (H+L) (antibody)

RRID:AB_2339800

This unknown targets Rat IgG (H+L)

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