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

@article{Park2002ExtentOC,
  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},
  journal={Science},
  year={2002},
  volume={298},
  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.

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