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Proceedings of the National Academy of Sciences
Article . 2012 . Peer-reviewed
Data sources: Crossref
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Integrative analysis of the zinc finger transcription factor Lame duck in the Drosophila myogenic gene regulatory network

Authors: Caitlin E. Gamble; Leila Shokri; Martha L. Bulyk; Martha L. Bulyk; Ting Ni; Kevin R. Rogacki; Brian W. Busser; +6 Authors

Integrative analysis of the zinc finger transcription factor Lame duck in the Drosophila myogenic gene regulatory network

Abstract

Contemporary high-throughput technologies permit the rapid identification of transcription factor (TF) target genes on a genome-wide scale, yet the functional significance of TFs requires knowledge of target gene expression patterns, cooperating TFs, and cis -regulatory element (CRE) structures. Here we investigated the myogenic regulatory network downstream of the Drosophila zinc finger TF Lame duck (Lmd) by combining both previously published and newly performed genomic data sets, including ChIP sequencing (ChIP-seq), genome-wide mRNA profiling, cell-specific expression patterns of putative transcriptional targets, analysis of histone mark signatures, studies of TF cooccupancy by additional mesodermal regulators, TF binding site determination using protein binding microarrays (PBMs), and machine learning of candidate CRE motif compositions. Our findings suggest that Lmd orchestrates an extensive myogenic regulatory network, a conclusion supported by the identification of Lmd-dependent genes, histone signatures of Lmd-bound genomic regions, and the relationship of these features to cell-specific gene expression patterns. The heterogeneous cooccupancy of Lmd-bound regions with additional mesodermal regulators revealed that different transcriptional inputs are used to mediate similar myogenic gene expression patterns. Machine learning further demonstrated diverse combinatorial motif patterns within tissue-specific Lmd-bound regions. PBM analysis established the complete spectrum of Lmd DNA binding specificities, and site-directed mutagenesis of Lmd and additional newly discovered motifs in known enhancers demonstrated the critical role of these TF binding sites in supporting full enhancer activity. Collectively, these findings provide insights into the transcriptional codes regulating muscle gene expression and offer a generalizable approach for similar studies in other systems.

Keywords

570, Binding Sites, Base Sequence, Systems Biology, Genome, Insect, Molecular Sequence Data, Gene Expression Regulation, Developmental, DNA, Muscle Development, Animals, Genetically Modified, Mesoderm, Myoblasts, Drosophila melanogaster, Enhancer Elements, Genetic, Myogenic Regulatory Factors, Artificial Intelligence, Animals, Drosophila Proteins, Gene Regulatory Networks, Transcriptome

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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
22
Average
Average
Top 10%
bronze