Identification of Functional Elements and Regulatory Circuits by Drosophila modENCODE

Abstract

To gain insight into how genomic information is translated into cellular and developmental programs, the Drosophila model organism Encyclopedia of DNA Elements (modENCODE) project is comprehensively mapping transcripts, histone modifications, chromosomal proteins, transcription factors, replication proteins and intermediates, and nucleosome properties across a developmental time course and in multiple cell lines. We have generated more than 700 data sets and discovered protein-coding, noncoding, RNA regulatory, replication, and chromatin elements, more than tripling the annotated portion of the Drosophila genome. Correlated activity patterns of these elements reveal a functional regulatory network, which predicts putative new functions for genes, reveals stage- and tissue-specific regulators, and enables gene-expression prediction. Our results provide a foundation for directed experimental and computational studies in Drosophila and related species and also a model for systematic data integration toward comprehensive genomic and functional annotation.

The TAGteam motif facilitates binding of 21 sequence-specific transcription factors in the Drosophila embryo

“…Depletion of zygotically transcribed Vielfaltig results in chromosome segregation and DNA replication defects (Staudt et al 2006), leading us to hypothesize that TAGteam motifs might play a role in ORC positioning. Using published ORC ChIPseq data from mixed-stage embryos (Roy et al 2010), we confirmed previous reports (MacAlpine et al 2010) of a strong correlation between chromatin accessibility and ORC binding. However, to our surprise, the presence of a TAGteam motif near ChIP peaks was associated with a lower level of ORC binding (Fig.…”

“…Genome-wide chromatin immunoprecipitation (ChIP) experiments in diverse metazoans have shown that many transcription factors bind thousands of highly overlapping loci in undifferentiated cells (Boyer et al 2005;Moorman et al 2006;Zeitlinger et al 2007;Chen et al 2008;Li et al 2008;Marson et al 2008;Bradley et al 2010;Gerstein et al 2010;Roy et al 2010;He et al 2011;Negre et al 2011). Many known enhancers of gene expression are bound by multiple transcription factors, suggesting that highly overlapping transcription factor binding may imply cis-regulatory potential.…”

“…The Drosophila origin recognition complex (ORC) preferentially binds regions with open chromatin (MacAlpine et al 2010), can interact with multiple transcription factors (Bosco et al 2001;Beall et al 2002;Dominguez-Sola et al 2007), and reportedly localizes to regions with high levels of overlapping transcription factor binding (Roy et al 2010). Depletion of zygotically transcribed Vielfaltig results in chromosome segregation and DNA replication defects (Staudt et al 2006), leading us to hypothesize that TAGteam motifs might play a role in ORC positioning.…”

“…Wiggle files for DNase I sensitivity measurements were downloaded from the UCSC Genome Browser FTP site (ftp://hgdownload.cse.ucsc.edu/ goldenPath); raw sequencing reads are available from the SRA (project SRP002474) . Wiggle files for the ORC data set (Roy et al 2010) were downloaded from the NCBI Sequence Read Archive (SRA) (accession number GSM694124). ChIP-seq binding data for six anterior-posterior transcription factors (Bradley et al 2010) was obtained from the NCBI Gene Expression Omnibus (GEO) database (accession number GSE20369).…”

“…ChIP-seq binding data for six anterior-posterior transcription factors (Bradley et al 2010) was obtained from the NCBI Gene Expression Omnibus (GEO) database (accession number GSE20369). When multiple data sets were available (e.g., ChIP data sets for multiple antibodies, or technical replicates), we used the data sets analyzed in the original publications (MacArthur et al 2009;Bradley et al 2010;Roy et al 2010;Li et al 2011). …”