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

Kageyama, Yuji; Mengus, Gabrielle; Gilfillan, Gregor D.; Kennedy, Hilda; Stuckenholz, Carsten; Kelley, R. L.; Becker, Peter B.; Kuroda, Mitzi I.

doi:10.1093/emboj/20.9.2236

Cited by 100 publications

(121 citation statements)

References 40 publications

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“…4). Recently, a similar enrichment of MSLs was observed at rox1 (23). A segment of the 3Ј end of the Pgd gene also shows a reproducible but modest enrichment for the MSL complex.…”

Section: Lysine 16 Acetylation Is Enriched Along the Length Of Dosagesupporting

confidence: 56%

“…The MSL complex is found at either of the two roX genes when these are moved to ectopic autosomal sites and spreads in cis from the transgenes to new sequences. The association of the complex with the roX transgenes occurs even when the latter are not transcribing, suggesting that the roX genes are not only sites of assembly for the complex but are also entry sites (14,16,23).…”

Section: Lysine 16 Acetylation Is Enriched Along the Length Of Dosagementioning

confidence: 99%

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Linking Global Histone Acetylation to the Transcription Enhancement of X-chromosomal Genes in Drosophila Males

Smith¹,

Allis²,

Lucchesi³

2001

Journal of Biological Chemistry

148

150

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It has become well established for several genes that targeting of histone acetylation to promoters is required for the activation of transcription. In contrast, global patterns of acetylation have not been ascribed to any particular regulatory function. In Drosophila, a specific modification of H4, acetylation at lysine 16, is enriched at hundreds of sites on the male X chromosome due to the activity of the male-specific lethal (MSL) dosage compensation complex. Utilizing chromatin immunoprecipitation, we have determined that H4Ac16 is present along the entire length of X-linked genes targeted by the MSL complex with relatively modest levels of acetylation at the promoter regions and high levels in the middle and/or 3 end of the transcription units. We propose that global acetylation by the MSL complex increases the expression of X-linked genes by facilitating transcription elongation rather than by enhancing promoter accessibility. We have also determined that H4Ac16 is absent from a region of the X chromosome that includes a gene known to be dosage-compensated by a MSL-independent mechanism. This study represents the first biochemical interpretation of the very large body of cytological observations on the chromosomal distribution of the MSL complex.Many post-translational modifications of the highly conserved histone N-terminal tails are linked to transcriptional regulation (1), with the most widely studied modification being acetylation of histones H3 and H4. Genetic and biochemical data have demonstrated that histone acetyltransferases such as yGcn5p and yEsa1p are recruited to the promoters of specific genes for the activation of transcription (2-6). Loss of function mutations of the genes encoding these enzymes, however, reveal that they are also responsible for a broad pattern of acetylation with relatively modest effects on the level of transcription (2, 4, 6).In Drosophila, evidence for special roles for particular histone modifications was revealed with antisera to specific isoforms of H4. While H4 isoforms acetylated at lysine 5 or 8 are associated with numerous sites throughout the genome, H4 acetylated at lysine 12 is enriched in chromocentric heterochromatin, and H4 acetylated at lysine 16 (H4Ac16) is exclusively associated with the male X chromosome (7, 8). Male-specific acetylation of H4 at lysine 16 is mediated by males absent on the first (MOF), 1 a MYST-family histone acetyltransferase present in the male-specific lethal (MSL) complex (9 -11). This histone acetyltransferase-containing complex is responsible for the dosage compensation of many X-linked genes by increasing their transcription in males to achieve a level of gene product equivalent to that generated by the two X chromosomes in females. In addition to its protein subunits, the MSL complex contains one of two nontranslated RNAs, roX1 and roX2 (11-15). Current models suggest that functional complexes form at the sites of transcription of these RNAs, then access the X chromosome at a small number of additional entry sites and subseq...

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“…4). Recently, a similar enrichment of MSLs was observed at rox1 (23). A segment of the 3Ј end of the Pgd gene also shows a reproducible but modest enrichment for the MSL complex.…”

Section: Lysine 16 Acetylation Is Enriched Along the Length Of Dosagesupporting

confidence: 56%

Section: Lysine 16 Acetylation Is Enriched Along the Length Of Dosagementioning

confidence: 99%

Linking Global Histone Acetylation to the Transcription Enhancement of X-chromosomal Genes in Drosophila Males

Smith¹,

Allis²,

Lucchesi³

2001

Journal of Biological Chemistry

148

150

View full text Add to dashboard Cite

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“…ChIP was performed as described previously, including purification over a CsCl gradient (Kageyama et al 2001). For control purposes, chromatin was also prepared using a CsCl-free protocol (Schwartz et al 2005), but no differences to CsCl-prepared chromatin were seen (data available on request).…”

Section: Chipmentioning

confidence: 99%

Chromosome-wide gene-specific targeting of theDrosophiladosage compensation complex

Gilfillan¹,

Straub²,

Wit³

et al. 2006

Genes Dev.

148

209

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The dosage compensation complex (DCC) of Drosophila melanogaster is capable of distinguishing the single male X from the other chromosomes in the nucleus. It selectively interacts in a discontinuous pattern with much of the X chromosome. How the DCC identifies and binds the X, including binding to the many genes that require dosage compensation, is currently unknown. To identify bound genes and attempt to isolate the targeting cues, we visualized male-specific lethal 1 (MSL1) protein binding along the X chromosome by combining chromatin immunoprecipitation with high-resolution microarrays. More than 700 binding regions for the DCC were observed, encompassing more than half the genes found on the X chromosome. In addition, several rare autosomal binding sites were identified. Essential genes are preferred targets, and genes binding high levels of DCC appear to experience the most compensation (i.e., greatest increase in expression). DCC binding clearly favors genes over intergenic regions, and binds most strongly to the 3 end of transcription units. Within the targeted genes, the DCC exhibits a strong preference for exons and coding sequences. Our results demonstrate gene-specific binding of the DCC, and identify several sequence elements that may partly direct its targeting.[Keywords: Transcription; histone modification; chromatin remodeling; MSL complex; microarray; gene expression] Supplemental material is available at http://www.genesdev.org.

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“…While it is possible that NURF is required for global aspects of higher order chromosome morphology that are needed to maintain normal male X chromosome structure, other local or transcription-based mechanisms could also account for the nurf301 and iswi phenotypes. The dosage compensation machinery is recruited to the male X chromosome at specific, high affinity sites or entry points and subsequently spreads into flanking chromatin (Kageyama et al 2001). NURF may regulate chromatin accessibility at one or a number of these initiation sites.…”

Section: Nurf Maintains Normal Sex Chromosome Morphologymentioning

confidence: 99%

Biological functions of the ISWI chromatin remodeling complex NURF

Badenhorst

Voas²,

Rebay³

et al. 2002

Genes Dev.

212

203

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The nucleosome remodeling factor (NURF) is one of several ISWI-containing protein complexes that catalyze ATP-dependent nucleosome sliding and facilitate transcription of chromatin in vitro. To establish the physiological requirements of NURF, and to distinguish NURF genetically from other ISWI-containing complexes, we isolated mutations in the gene encoding the large NURF subunit, nurf301. We confirm that NURF is required for transcription activation in vivo. In animals lacking NURF301, heat-shock transcription factor binding to and transcription of the hsp70 and hsp26 genes are impaired. Additionally, we show that NURF is required for homeotic gene expression. Consistent with this, nurf301 mutants recapitulate the phenotypes of Enhancer of bithorax, a positive regulator of the Bithorax-Complex previously localized to the same genetic interval. Finally, mutants in NURF subunits exhibit neoplastic transformation of larval blood cells that causes melanotic tumors to form.

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

Cited by 100 publications

References 40 publications

Linking Global Histone Acetylation to the Transcription Enhancement of X-chromosomal Genes in Drosophila Males

Linking Global Histone Acetylation to the Transcription Enhancement of X-chromosomal Genes in Drosophila Males

Chromosome-wide gene-specific targeting of theDrosophiladosage compensation complex

Biological functions of the ISWI chromatin remodeling complex NURF

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