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A condensin-like dosage compensation complex acts at a distance to control expression throughout the genome.
Genes Dev. 2009 Mar 01; 23(5):602-18.GD

Abstract

In many species, a dosage compensation complex (DCC) is targeted to X chromosomes of one sex to equalize levels of X-gene products between males (1X) and females (2X). Here we identify cis-acting regulatory elements that target the Caenorhabditis elegans X chromosome for repression by the DCC. The DCC binds to discrete, dispersed sites on X of two types. rex sites (recruitment elements on X) recruit the DCC in an autonomous, DNA sequence-dependent manner using a 12-base-pair (bp) consensus motif that is enriched on X. This motif is critical for DCC binding, is clustered in rex sites, and confers much of X-chromosome specificity. Motif variants enriched on X by 3.8-fold or more are highly predictive (95%) for rex sites. In contrast, dox sites (dependent on X) lack the X-enriched variants and cannot bind the DCC when detached from X. dox sites are more prevalent than rex sites and, unlike rex sites, reside preferentially in promoters of some expressed genes. These findings fulfill predictions for a targeting model in which the DCC binds to recruitment sites on X and disperses to discrete sites lacking autonomous recruitment ability. To relate DCC binding to function, we identified dosage-compensated and noncompensated genes on X. Unexpectedly, many genes of both types have bound DCC, but many do not, suggesting the DCC acts over long distances to repress X-gene expression. Remarkably, the DCC binds to autosomes, but at far fewer sites and rarely at consensus motifs. DCC disruption causes opposite effects on expression of X and autosomal genes. The DCC thus acts at a distance to impact expression throughout the genome.

Authors+Show Affiliations

Howard Hughes Medical Institute, Department of Molecular and Cell Biology, University of California at Berkeley, Berkeley, California 97420, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

19270160

Citation

Jans, Judith, et al. "A Condensin-like Dosage Compensation Complex Acts at a Distance to Control Expression Throughout the Genome." Genes & Development, vol. 23, no. 5, 2009, pp. 602-18.
Jans J, Gladden JM, Ralston EJ, et al. A condensin-like dosage compensation complex acts at a distance to control expression throughout the genome. Genes Dev. 2009;23(5):602-18.
Jans, J., Gladden, J. M., Ralston, E. J., Pickle, C. S., Michel, A. H., Pferdehirt, R. R., Eisen, M. B., & Meyer, B. J. (2009). A condensin-like dosage compensation complex acts at a distance to control expression throughout the genome. Genes & Development, 23(5), 602-18. https://doi.org/10.1101/gad.1751109
Jans J, et al. A Condensin-like Dosage Compensation Complex Acts at a Distance to Control Expression Throughout the Genome. Genes Dev. 2009 Mar 1;23(5):602-18. PubMed PMID: 19270160.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A condensin-like dosage compensation complex acts at a distance to control expression throughout the genome. AU - Jans,Judith, AU - Gladden,John M, AU - Ralston,Edward J, AU - Pickle,Catherine S, AU - Michel,Agnès H, AU - Pferdehirt,Rebecca R, AU - Eisen,Michael B, AU - Meyer,Barbara J, PY - 2009/3/10/entrez PY - 2009/3/10/pubmed PY - 2009/3/12/medline SP - 602 EP - 18 JF - Genes & development JO - Genes Dev. VL - 23 IS - 5 N2 - In many species, a dosage compensation complex (DCC) is targeted to X chromosomes of one sex to equalize levels of X-gene products between males (1X) and females (2X). Here we identify cis-acting regulatory elements that target the Caenorhabditis elegans X chromosome for repression by the DCC. The DCC binds to discrete, dispersed sites on X of two types. rex sites (recruitment elements on X) recruit the DCC in an autonomous, DNA sequence-dependent manner using a 12-base-pair (bp) consensus motif that is enriched on X. This motif is critical for DCC binding, is clustered in rex sites, and confers much of X-chromosome specificity. Motif variants enriched on X by 3.8-fold or more are highly predictive (95%) for rex sites. In contrast, dox sites (dependent on X) lack the X-enriched variants and cannot bind the DCC when detached from X. dox sites are more prevalent than rex sites and, unlike rex sites, reside preferentially in promoters of some expressed genes. These findings fulfill predictions for a targeting model in which the DCC binds to recruitment sites on X and disperses to discrete sites lacking autonomous recruitment ability. To relate DCC binding to function, we identified dosage-compensated and noncompensated genes on X. Unexpectedly, many genes of both types have bound DCC, but many do not, suggesting the DCC acts over long distances to repress X-gene expression. Remarkably, the DCC binds to autosomes, but at far fewer sites and rarely at consensus motifs. DCC disruption causes opposite effects on expression of X and autosomal genes. The DCC thus acts at a distance to impact expression throughout the genome. SN - 1549-5477 UR - https://www.unboundmedicine.com/medline/citation/19270160/A_condensin_like_dosage_compensation_complex_acts_at_a_distance_to_control_expression_throughout_the_genome_ L2 - http://www.genesdev.org/cgi/pmidlookup?view=long&pmid=19270160 DB - PRIME DP - Unbound Medicine ER -