Condensin controls cellular RNA levels through the accurate segregation of chromosomes instead of directly regulating transcription
- CNRS, France
- MRC London Institute of Medical Sciences (LMS), United Kingdom
- European Molecular Biology Laboratory, Germany
Abstract
Condensins are genome organisers that shape chromosomes and promote their accurate transmission. Several studies have also implicated condensins in gene expression, although any mechanisms have remained enigmatic. Here, we report on the role of condensin in gene expression in fission and budding yeasts. In contrast to previous studies, we provide compelling evidence that condensin plays no direct role in the maintenance of the transcriptome, neither during interphase nor during mitosis. We further show that the changes in gene expression in post-mitotic fission yeast cells that result from condensin inactivation are largely a consequence of chromosome missegregation during anaphase, which notably depletes the RNA-exosome from daughter cells. Crucially, preventing karyotype abnormalities in daughter cells restores a normal transcriptome despite condensin inactivation. Thus, chromosome instability, rather than a direct role of condensin in the transcription process, changes gene expression. This knowledge challenges the concept of gene regulation by canonical condensin complexes.
Data availability
RNA-seq data are accessible from the Gene Expression Omnibus (GEO) database under the accession number GSE112281.Microarrays data are available as supplemental table in excel format
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Condensin controls cellular RNA levels through the accurate segregation of chromosomes instead of directly regulating transcriptionPublicly available at the NCBI Gene Expression Omnibus (accession no: GSE112281).
Article and author information
Author details
Sara Cuylen-Haering
Christian H Haering
Funding
Centre National de la Recherche Scientifique
- Pascal Bernard
Agence Nationale de la Recherche (ANR-15-CE12-0002-01)
- Xavier Robellet
- Pascal Bernard
Fondation ARC pour la Recherche sur le Cancer (PJA 20151203343)
- Pascal Bernard
Ligue Régionale Contre le Cancer - comité du Rhône
- Pascal Bernard
Medical Research Council
- Xi-Ming Sun
- Samuel Marguerat
European Molecular Biology Laboratory
- Sara Cuylen-Haering
- Sandra Clauder-Münster
- Lars Steinmetz
- Christian H Haering
Fondation pour la Recherche Médicale (FDT20170437039)
- Clémence Hocquet
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Job Dekker, University of Massachusetts Medical School, United States
Version history
- Received: May 20, 2018
- Accepted: September 18, 2018
- Accepted Manuscript published: September 19, 2018 (version 1)
- Version of Record published: October 5, 2018 (version 2)
Copyright
© 2018, Hocquet et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Condensin controls cellular RNA levels through the accurate segregation of chromosomes instead of directly regulating transcription
eLife 7:e38517.
https://doi.org/10.7554/eLife.38517
Further reading
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- Cell Biology
- Chromosomes and Gene Expression
The cohesin complex plays essential roles in chromosome segregation, 3D genome organisation, and DNA damage repair through its ability to modify DNA topology. In higher eukaryotes, meiotic chromosome function, and therefore fertility, requires cohesin complexes containing meiosis-specific kleisin subunits: REC8 and RAD21L in mammals and REC-8 and COH-3/4 in Caenorhabditis elegans. How these complexes perform the multiple functions of cohesin during meiosis and whether this involves different modes of DNA binding or dynamic association with chromosomes is poorly understood. Combining time-resolved methods of protein removal with live imaging and exploiting the temporospatial organisation of the C. elegans germline, we show that REC-8 complexes provide sister chromatid cohesion (SCC) and DNA repair, while COH-3/4 complexes control higher-order chromosome structure. High-abundance COH-3/4 complexes associate dynamically with individual chromatids in a manner dependent on cohesin loading (SCC-2) and removal (WAPL-1) factors. In contrast, low-abundance REC-8 complexes associate stably with chromosomes, tethering sister chromatids from S-phase until the meiotic divisions. Our results reveal that kleisin identity determines the function of meiotic cohesin by controlling the mode and regulation of cohesin–DNA association, and are consistent with a model in which SCC and DNA looping are performed by variant cohesin complexes that coexist on chromosomes.
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- Chromosomes and Gene Expression
- Developmental Biology
Though long non-coding RNAs (lncRNAs) represent a substantial fraction of the Pol II transcripts in multicellular animals, only a few have known functions. Here we report that the blocking activity of the Bithorax complex (BX-C) Fub-1 boundary is segmentally regulated by its own lncRNA. The Fub-1 boundary is located between the Ultrabithorax (Ubx) gene and the bxd/pbx regulatory domain, which is responsible for regulating Ubx expression in parasegment PS6/segment A1. Fub-1 consists of two hypersensitive sites, HS1 and HS2. HS1 is an insulator while HS2 functions primarily as an lncRNA promoter. To activate Ubx expression in PS6/A1, enhancers in the bxd/pbx domain must be able to bypass Fub-1 blocking activity. We show that the expression of the Fub-1 lncRNAs in PS6/A1 from the HS2 promoter inactivates Fub-1 insulating activity. Inactivation is due to read-through as the HS2 promoter must be directed toward HS1 to disrupt blocking.
