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ModENCODE Studies Offer Clues to Genome Regulation in Model Organisms

NEW YORK (GenomeWeb) – A set of studies published in Genome Research today outlines findings from the modENCODE project, an effort aimed at identifying and understanding regulatory elements in the genomes of fruit fly and Caenorhabditis elegans worm model organisms.

The half dozen articles appearing in the online and print versions of the journal explore the functional elements involved in cellular processes such as DNA replication and transcription, along with those contributing to various aspects of Drosophila melanogaster and C. elegans embryonic development.

In one of the studies, for example, University of California at Berkeley researchers used transcriptome sequencing to track down genes contributing to various stages of development in Drosophila and C. elegans.

When they sequenced and compared RNA transcripts in tissues from each model organism across dozens of stages of development, the investigators saw highly conserved patterns of gene expression — involving so-called "stage-associated genes" — despite the notable life cycle differences between the species, which are thought to have diverged from one another some 600 million years.

Other modENCODE investigators looked more closely at transcriptome features from just one of the model organisms.

For example, a team from the US and Singapore tallied up microRNAs, small interfering RNAs, and Piwi-interacting RNAs through deep sequencing experiments on dozens of small RNA libraries made from 25 Drosophila cell lines.

Meanwhile, researchers from the National Institutes of Health, Baylor College of Medicine, and elsewhere came up with an updated annotation of the Drosophila transcriptome using RNA sequencing data from 81 tissue types or developmental stages representing 15 Drosophila species.

That group also generated new draft genome sequences for eight of the species — information that's expected to prove useful for comparative genomic analyses of fruit flies.

In another modENCODE study, researchers from Duke University Medical Center focused on chromatin profiles associated with DNA replication and transcription processes. That team relied on a method called Repli-seq to peek at the chromatin features that characterize early and late replicating regions of the Drosophila genome.

In general, active histone marks and high gene density tend to appear within early replicating DNA, which is believed to comprise roughly one-third of the fruit fly genome. The more gene-poor, late replicating regions were more apt to harbor repressive rather than active histone marks.

The Duke researchers discovered that while most domains in the Drosophila genome can consistently be classified as either early or late replicating, a fraction of the regions they looked at were more dynamic — differences that appeared to be related to origin activation. For example, they found that early replication of the X chromosome in male fruit flies seems to depend on the modifications to the histone mark H4K16 and activity by the dosage compensation complex.

In two more newly published modENCODE papers, teams from the US and France examined genome-wide binding patterns for 84 transcription regulatory factors across the fruit fly genome and considered the distribution of one particular repressive histone mark in relation to duplicated genes in C. elegans and in four Drosophila species.

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