Genome-wide Analysis Reveals MOF as a Key Regulator of Dosage Compensation and Gene Expression in Drosophila

Kind, Jop; Vaquerizas, Juan M.; Gebhardt, Philipp; Gentzel, Marc; Luscombe, Nicholas M.; Bertone, Paul; Akhtar, Asifa

doi:10.1016/j.cell.2008.04.036

Cited by 146 publications

(203 citation statements)

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“…9A,B), in agreement with a function of this mark in transcriptional activation (Bell et al 2007;Kind et al 2008). However, even at inactive autosomal genes, zones of early replication also bear higher levels of H4K16 acetylation (Supplemental Fig.…”

Section: Acetylation Of H4k16 Marks Early Replicating Regions and Sitsupporting

confidence: 65%

“…Increased acetylation of H4K16 at the dosage-compensated X chromosome in Drosophila also leads to a decondensed polytene chromosome in vivo (Corona et al 2002). Importantly, however, H4K16 acetylation is also present on autosomes in flies (Bell et al 2007;Kind et al 2008) and at accessible chromatin in human cells in vivo (Shogren-Knaak et al 2006).…”

Section: Dynamic Replication Timing On Autosomes Correlates With Diffmentioning

confidence: 99%

“…The dosage-compensated X chromosome is associated with highly elevated levels of acetylation of Lys 16 of histone H4 (H4K16ac) as measured by immunofluorescence, polytene staining, and chromatin immunoprecipitation (ChIP) (Turner et al 1992;Smith et al 2001;Gilfillan et al 2006;Kind et al 2008). Importantly, acetylation of this particular lysine residue has been shown to directly interfere with higher-order chromatin compaction in vitro (Shogren-Knaak et al 2006).…”

Section: Dynamic Replication Timing On Autosomes Correlates With Diffmentioning

confidence: 99%

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Chromatin state marks cell-type- and gender-specific replication of the Drosophila genome

Schwaiger¹,

Stadler²,

Bell³

et al. 2009

Genes Dev.

146

265

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Duplication of eukaryotic genomes during S phase is coordinated in space and time. In order to identify zones of initiation and cell-type-as well as gender-specific plasticity of DNA replication, we profiled replication timing, histone acetylation, and transcription throughout the Drosophila genome. We observed two waves of replication initiation with many distinct zones firing in early-S phase and multiple, less defined peaks at the end of S phase, suggesting that initiation becomes more promiscuous in late-S phase. A comparison of different cell types revealed widespread plasticity of replication timing on autosomes. Most occur in large regions, but only half coincide with local differences in transcription. In contrast to confined autosomal differences, a global shift in replication timing occurs throughout the single male X chromosome. Unlike in females, the dosage-compensated X chromosome replicates almost exclusively early. This difference occurs at sites that are not transcriptionally hyperactivated, but show increased acetylation of Lys 16 of histone H4 (H4K16ac). This suggests a transcription-independent, yet chromosome-wide process related to chromatin. Importantly, H4K16ac is also enriched at initiation zones as well as early replicating regions on autosomes during S phase. Together, our study reveals novel organizational principles of DNA replication of the Drosophila genome and suggests that H4K16ac is more closely correlated with replication timing than is transcription.[Keywords: Chromatin; Drosophila; microarray; replication] Supplemental material is available at http://www.genesdev.org.

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Section: Acetylation Of H4k16 Marks Early Replicating Regions and Sitsupporting

confidence: 65%

Section: Dynamic Replication Timing On Autosomes Correlates With Diffmentioning

confidence: 99%

Section: Dynamic Replication Timing On Autosomes Correlates With Diffmentioning

confidence: 99%

See 1 more Smart Citation

Chromatin state marks cell-type- and gender-specific replication of the Drosophila genome

Schwaiger¹,

Stadler²,

Bell³

et al. 2009

Genes Dev.

146

265

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show abstract

“…This is Fig 5C), suggesting that a similar set of genes is being targeted by the dosage compensation complex on the X in both species. Finally, our metagene analysis of the H4K16ac mark reveals a distinctive 3' bias specifically over active X-linked gene bodies (Fig 5D), consistent with the pattern mediated by the MSL complex in D. melanogaster [46,48]. Taken together, these results suggest that D. busckii shares the same mechanism of dosage compensation for the ancestral X chromosome as D. melanogaster, despite their distant phylogenetic relationship (Fig 2) and their different sex chromosome karyotype.…”

Section: Transcriptomic and Epigenomic Evolution Of The Neo-ysupporting

confidence: 67%

Ancestral chromatin configuration constrains chromatin evolution on differentiating sex chromosomes inDrosophila

Zhou

Bachtrog

2015

Preprint

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Sex chromosomes evolve distinctive types of chromatin from a pair of ancestral autosomes that are usually euchromatic. In Drosophila, the dosage-compensated X becomes enriched for hyperactive chromatin in males (mediated by H4K16ac), while the Y chromosome acquires silencing heterochromatin (enriched for H3K9me2/3). Drosophila autosomes are typically mostly euchromatic but the small dot chromosome has evolved a heterochromatinlike milieu (enriched for H3K9me2/3) that permits the normal expression of dot-linked genes, but which is different from typical pericentric heterochromatin. In Drosophila busckii, the dot chromosomes have fused to the ancestral sex chromosomes, creating a pair of 'neo-sex' chromosomes. Here we collect genomic, transcriptomic and epigenomic data from D. busckii, to investigate the evolutionary trajectory of sex chromosomes from a largely heterochromatic ancestor. We show that the neo-sex chromosomes formed <1 million years ago, but nearly 60% of neo-Y linked genes have already become non-functional. Expression levels are generally lower for the neo-Y alleles relative to their neo-X homologs, and the silencing heterochromatin mark H3K9me2, but not H3K9me3, is significantly enriched on silenced neo-Y genes. Despite rampant neo-Y degeneration, we find that the neo-X is deficient for the canonical histone modification mark of dosage compensation (H4K16ac), relative to autosomes or the compensated ancestral X chromosome, possibly reflecting constraints imposed on evolving hyperactive chromatin in an originally heterochromatic environment. Yet, neo-X genes are transcriptionally more active in males, relative to females, suggesting the evolution of incipient dosage compensation on the neo-X. Our data show that Y degeneration proceeds quickly after sex chromosomes become established through genomic and epigenetic changes, and are consistent with the idea that the evolution of sex-linked chromatin is influenced by its ancestral configuration. Data Availability Statement: All sequencing reads, the genome sequence assembly and annotation generated in this study are deposited at the National Center for Biotechnology Information Short Reads Archive (www.ncbi.nlm.nih.gov/sra) under the Bioproject accession no. PRJNA274996.Funding: This work was funded by NIH grants (R01GM076007, R01GM093182 and R01GM101255) to DB. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Author SummaryDNA is packaged with proteins into two general types of chromatin: the transcriptionally active euchromatin and repressive heterochromatin. Sex chromosomes typically evolve from a pair of euchromatic autosomes. The Y chromosome of Drosophila is gene poor and almost entirely heterochromatic; the X chromosome, in contrast, has evolved a hyperactive euchromatin structure and globally up-regulates its gene expression, to compensate for loss of activity from the homologous genes on the Y chromosome. The evolutionary trajectory along which sex chromosomes...

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“…MOF is an integral member of the DCC and is enriched on the male X chromosome. In addition, MOF is more modestly enriched at the 59 end of transcribed genes throughout the genomes of both sexes (Kind et al 2008). In spite of the general role of these two factors, mutations in mle and mof are lethal only to males.…”

mentioning

confidence: 99%

Coordinated Regulation of Heterochromatic Genes inDrosophila melanogasterMales

et al. 2009

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Dosage compensation modifies the chromatin of X-linked genes to assure equivalent expression in sexes with unequal X chromosome dosage. In Drosophila dosage compensation is achieved by increasing expression from the male X chromosome. The ribonucleoprotein dosage compensation complex (DCC) binds hundreds of sites along the X chromosome and modifies chromatin to facilitate transcription. Loss of roX RNA, an essential component of the DCC, reduces expression from X-linked genes. Surprisingly, loss of roX RNA also reduces expression from genes situated in proximal heterochromatin and on the small, heterochromatic fourth chromosome. Mutation of some, but not all, of the genes encoding DCC proteins produces a similar effect. Reduction of roX function suppresses position effect variegation (PEV), revealing functional alteration in heterochromatin. The effects of roX mutations on heterochromatic gene expression and PEV are limited to males. A sex-limited role for the roX RNAs in autosomal gene expression was unexpected. We propose that this reflects a difference in the heterochromatin of males and females, which serves to accommodate the heterochromatic Y chromosome present in the male nucleus. roX transcripts may thus participate in two distinct regulatory systems that have evolved in response to highly differentiated sex chromosomes: compensation of X-linked gene dosage and modulation of heterochromatin.

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Genome-wide Analysis Reveals MOF as a Key Regulator of Dosage Compensation and Gene Expression in Drosophila

Cited by 146 publications

References 46 publications

Chromatin state marks cell-type- and gender-specific replication of the Drosophila genome

Chromatin state marks cell-type- and gender-specific replication of the Drosophila genome

Ancestral chromatin configuration constrains chromatin evolution on differentiating sex chromosomes inDrosophila

Coordinated Regulation of Heterochromatic Genes inDrosophila melanogasterMales

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