X Chromosome Sites Autonomously Recruit the Dosage Compensation Complex in Drosophila Males

ABSTRACTOver 50 years ago, Susumo Ohno proposed that dosage compensation in mammals would require upregulation of gene expression on the single active X chromosome, a mechanism which to date is best understood in the fruit fly Drosophila melanogaster. Here, we report that the GA-repeat sequences that recruit the conserved MSL dosage compensation complex to the Drosophila X chromosome are also enriched across mammalian X chromosomes, providing genomic support for the Ohno hypothesis. We show that mammalian GA-repeats derive in part from transposable elements, suggesting a mechanism whereby unrelated X chromosomes from dipterans to mammals accumulate binding sites for the MSL dosage compensation complex through convergent evolution, driven by their propensity to accumulate transposable elements.

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The Caenorhabditis elegans Dosage Compensation Machinery Is Recruited to X Chromosome DNA Attached to an Autosome

Genetics ◽

10.1093/genetics/156.4.1603 ◽

2000 ◽

Vol 156 (4) ◽

pp. 1603-1621

Author(s):

Jason D Lieb ◽

Carlos Ortiz de Solorzano ◽

Enrique Garcia Rodriguez ◽

Arthur Jones ◽

Michael Angelo ◽

...

Keyword(s):

Caenorhabditis Elegans ◽

X Chromosome ◽

Dosage Compensation ◽

Dna Sequences ◽

Three Dimensional ◽

Dosage Compensation Complex ◽

X Chromosomes ◽

Cis Acting ◽

Recognition Elements ◽

The Right

Abstract The dosage compensation machinery of Caenorhabditis elegans is targeted specifically to the X chromosomes of hermaphrodites (XX) to reduce gene expression by half. Many of the trans-acting factors that direct the dosage compensation machinery to X have been identified, but none of the proposed cis-acting X chromosome-recognition elements needed to recruit dosage compensation components have been found. To study X chromosome recognition, we explored whether portions of an X chromosome attached to an autosome are competent to bind the C. elegans dosage compensation complex (DCC). To do so, we devised a three-dimensional in situ approach that allowed us to compare the volume, position, and number of chromosomal and subchromosomal bodies bound by the dosage compensation machinery in wild-type XX nuclei and XX nuclei carrying an X duplication. The dosage compensation complex was found to associate with a duplication of the right 30% of X, but the complex did not spread onto adjacent autosomal sequences. This result indicates that all the information required to specify X chromosome identity resides on the duplication and that the dosage compensation machinery can localize to a site distinct from the full-length hermaphrodite X chromosome. In contrast, smaller duplications of other regions of X appeared to not support localization of the DCC. In a separate effort to identify cis-acting X recognition elements, we used a computational approach to analyze genomic DNA sequences for the presence of short motifs that were abundant and overrepresented on X relative to autosomes. Fourteen families of X-enriched motifs were discovered and mapped onto the X chromosome.

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Interactions between dosage compensation complex components Msl-1, Msl-2 and NURF component NURF301 with long non-coding RNA gene hsrω

10.1101/515726 ◽

2019 ◽

Author(s):

Deo Prakash Chaturvedi

Keyword(s):

X Chromosome ◽

Dosage Compensation ◽

Dosage Compensation Complex ◽

Chromatin Remodeler ◽

Down Regulation ◽

Over Expression ◽

Non Coding Rna ◽

Crucial Component ◽

Male Specific ◽

Long Non Coding Rna

AbstractHyperactivity of the single X-chromosome in male Drosophila is achieved by establishing a ribonucleoprotein complex, called Dosage Compensation Complex (DCC), on the male X chromosome. Msl-1 and Msl-2 proteins, involved in the initiation and establishing of DCC on male X chromosome, are very crucial component of this complex. In the present study, it has been found here that a long non-coding RNA gene hsrω genetically interacts with Msl-1 as well as Msl-2 and suppresses the lethal phenotype of Msl-1 or Msl-2 down-regulation in its up-regulated background. Additionally, it is also found here that an ATP-dependent chromatin remodeler, NURF301, also interacts with hsrω in same manner. General lethality caused by Act-GAL4 driven global expression of NURF301-RNAi and the male-specific lethality following Msl-1-RNAi or Msl-2-RNAi transgene expression were partially suppressed by over-expression of hsrω, but not by down regulation through hsrω-RNAi. Likewise, eye phenotypes following ey-GAL4 driven down-regulation of NURF301 or Msl-1 or Msl-2 were also partially suppressed by over-expression of hsrω. Act-GAL4 driven global over-expression of hsrω along with Msl-1-RNAi or Msl-2-RNAi transgene substantially restored levels of MSL-2 protein on the male X chromosome. Similarly, levels and distribution of Megator protein, which was reduced and distribution at nuclear rim and in nucleoplasm was affected in the MT and SG nuclei, is also restored when hsrω transcripts are down-regulated in Act-GAL4 driven Msl-1-RNAi or Msl-2-RNAi genetic background. NURF301, a known chromatin remodeler, when down-regulated shows decondensed X chromosome in male larvae. Down-regulation of hsrω results in restoration of chromosome architecture without affecting the level of ISWI protein-another chromatin remodeler protein, known to interacting with hsrω.

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Sex-Specific Assembly of a Dosage Compensation Complex on the Nematode X Chromosome

Science ◽

10.1126/science.274.5293.1736 ◽

1996 ◽

Vol 274 (5293) ◽

pp. 1736-1739 ◽

Cited By ~ 82

Author(s):

P.-T. Chuang ◽

J. D. Lieb ◽

B. J. Meyer

Keyword(s):

X Chromosome ◽

Dosage Compensation ◽

Dosage Compensation Complex

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Two Classes of Dosage Compensation Complex Binding Elements along Caenorhabditis elegans X Chromosomes

Molecular and Cellular Biology ◽

10.1128/mcb.01448-08 ◽

2009 ◽

Vol 29 (8) ◽

pp. 2023-2031 ◽

Cited By ~ 6

Author(s):

Timothy A. Blauwkamp ◽

Gyorgyi Csankovszki

Keyword(s):

Caenorhabditis Elegans ◽

X Chromosome ◽

Dosage Compensation ◽

Gene Products ◽

Dosage Compensation Complex ◽

X Chromosomes ◽

Linked Gene ◽

Unknown Mechanism

ABSTRACT Dosage compensation equalizes X-linked gene products between the sexes. In Caenorhabditis elegans, the dosage compensation complex (DCC) binds both X chromosomes in XX animals and halves the transcription from each. The DCC is recruited to the X chromosomes by a number of loci, rex sites, and is thought to spread from these sites by an unknown mechanism to cover the rest of the chromosome. Here we describe a novel class of DCC-binding elements that we propose serve as “way stations” for DCC binding and spreading. Both rex sites and way stations comprise strong foci of DCC binding on the native X chromosome. However, rex sites maintain their ability to bind large amounts of DCC even on X duplications detached from the native X, while way stations do not. These results suggest that two distinct classes of DCC-binding elements facilitate recruitment and spreading of the DCC along the X chromosome.

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Chromosome-wide mechanisms to decouple gene expression from gene dose during sex-chromosome evolution

eLife ◽

10.7554/elife.17365 ◽

2016 ◽

Vol 5 ◽

Cited By ~ 14

Author(s):

Bayly S Wheeler ◽

Erika Anderson ◽

Christian Frøkjær-Jensen ◽

Qian Bian ◽

Erik Jorgensen ◽

...

Keyword(s):

Gene Expression ◽

X Chromosome ◽

Dosage Compensation ◽

Chromosome Evolution ◽

Sex Chromosome ◽

Nuclear Periphery ◽

Single Copy ◽

Dosage Compensation Complex ◽

Gene Dose ◽

Caenorhabditis Elegans Genome

Changes in chromosome number impair fitness by disrupting the balance of gene expression. Here we analyze mechanisms to compensate for changes in gene dose that accompanied the evolution of sex chromosomes from autosomes. Using single-copy transgenes integrated throughout the Caenorhabditis elegans genome, we show that expression of all X-linked transgenes is balanced between XX hermaphrodites and XO males. However, proximity of a dosage compensation complex (DCC) binding site (rex site) is neither necessary to repress X-linked transgenes nor sufficient to repress transgenes on autosomes. Thus, X is broadly permissive for dosage compensation, and the DCC acts via a chromosome-wide mechanism to balance transcription between sexes. In contrast, no analogous X-chromosome-wide mechanism balances transcription between X and autosomes: expression of compensated hermaphrodite X-linked transgenes is half that of autosomal transgenes. Furthermore, our results argue against an X-chromosome dosage compensation model contingent upon rex-directed positioning of X relative to the nuclear periphery.

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