Extent of Chromatin Spreading Determined by roX RNA Recruitment of MSL Proteins

  title={Extent of Chromatin Spreading Determined by roX RNA Recruitment of MSL Proteins},
  author={Yongkyu Park and Richard L. Kelley and Hyangyee Oh and Mitzi I. Kuroda and Victoria H. Meller},
  pages={1620 - 1623}
The untranslated roX1 and roX2 RNAs are components of the Drosophila male-specific lethal (MSL) complex, which modifies histones to up-regulate transcription of the male X chromosome. roX genes are normally located on the X chromosome, and roX transgenes can misdirect the dosage compensation machinery to spread locally on other chromosomes. Here we define MSL protein abundance as a determinant of whether the MSL complex will spread in cis from an autosomalroX transgene. The number of expressed… 

Local spreading of MSL complexes from roX genes on the Drosophila X chromosome.

These results support a model for distribution of MSL complexes, in which local spreading in cis from roX genes is balanced with diffusion of soluble complexes in trans, by nucleation of spreading from their sites of synthesis.

Sequence‐specific targeting of MSL complex regulates transcription of the roX RNA genes

Surprisingly, the DHS is not required for initiation of cis spreading of MSL complex, instead local transcription of roX RNAs correlates with extensive spreading, and is found to counteracts constitutive repression at roX1, resulting in male‐specific expression of ro X1 RNA.

Sequence-specific targeting of Drosophila roX genes by the MSL dosage compensation complex.

Regional Control of Chromatin Organization by Noncoding roX RNAs and the NURF Remodeling Complex in Drosophila melanogaster

Strikingly, roX mutations suppress the Nurf mutant phenotype regionally on the male X chromosome, and a roX transgene induces disruption of local flanking autosomal chromatin in Nurf mutants, demonstrating the potent capability of roX genes to organize large chromatin domains in cis, on the X chromosome.

MSL complex associates with clusters of actively transcribed genes along the Drosophila male X chromosome.

It is hypothesize that after initial recruitment of the MSL complex to the X chromosome by unknown mechanisms, nascent transcripts or chromatin marks associated with active transcription attract the MSl complex to its final targets, and defining MSL-complex-binding sites will provide a tool for understanding functions of large noncoding RNAs that have remained elusive.

Path to equality strewn with roX.

Functional integration of the histone acetyltransferase MOF into the dosage compensation complex

It is found that contact of the MOF chromo‐related domain with roX RNA plays only a minor role in correct targeting to the X chromosome in vivo, and a strong, direct interaction between a conserved MSL1 domain and a zinc finger within MOF's HAT domain is crucial.

The MSL complex levels are critical for its correct targeting to the chromosomes in Drosophila melanogaster

Wild-type MSL complex titers are critical for correct targeting to the X chromosome in Drosophila, and support a model in whichMSL complex binding to theX is directed by a hierarchy of target sites that display different affinities for the MSL proteins.

MSL cis-spreading from roX gene up-regulates the neighboring genes.




Association and spreading of the Drosophila dosage compensation complex from a discrete roX1 chromatin entry site

A model for the targeted assembly of the MSL complex, in which initial binding occurs at ∼35 dispersed chromatin entry sites, followed by spreading in cis into flanking regions, is proposed and mapped the recruitment activity to a 217 bp roX1 fragment that shows male‐specific DNase hypersensitivity and can be preferentially cross‐linked in vivo to theMSL complex.

The roX genes encode redundant male‐specific lethal transcripts required for targeting of the MSL complex

Males can be rescued by roX cDNAs from autosomal transgenes, demonstrating the genetic separation of the chromatin entry and RNA‐encoding functions.

Role of the male specific lethal (msl) genes in modifying the effects of sex chromosomal dosage in Drosophila.

It is suggested that sequestration of the MSL proteins occurs in males to nullify on the autosomes and maintain on the X, an inverse effect produced by negatively acting dosage-dependent regulatory genes as a consequence of the evolution of the X/Y sex chromosomal system.

Recruitment of the Male-specific Lethal (MSL) Dosage Compensation Complex to an Autosomally Integrated roXChromatin Entry Site Correlates with an Increased Expression of an Adjacent Reporter Gene in Male Drosophila *

This study shows that insertion of either roX1 or roX2 DNA sequences, upstream of an insulated lacZ reporter gene controlled with the constitutive armadillo promoter, results in a significant elevation of expression of lacZ in males.

ATP-dependent remodeling and acetylation as regulators of chromatin fluidity.

This review focuses on ATP-dependent remodeling complexes and how these complexes interact with acetylation complexes to regulate gene expression.

Control of X chromosome transcription by the maleless gene in Drosophila

It is reported here that, reasoning that sex- specific lethal mutations may represent lesions in the processes controlling the transcription of X-linked loci, several male-specific lethal mutations are sought and recovered and it is noted that they affect the levels ofX-linked enzyme activities in crude extracts of homozygous male larvae.