ArticlePLoS genetics2010
Combinatorial binding leads to diverse regulatory responses: Lmd is a tissue-specific modulator of Mef2 activity.
Article in PLoS genetics, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 37 citations in OpenAlex.
- Enhanced expression of the myogenic factor Myocyte enhancer factor-2 in imaginal disc myoblasts activates a partial, but incomplete, muscle development program.Developmental biology · 2024Article
- DiPRO1 distinctly reprograms muscle and mesenchymal cancer cells.EMBO molecular medicine · 2024Article
- Simultaneous cellular and molecular phenotyping of embryonic mutants using single-cell regulatory trajectories.Developmental cell · 2022Article
- Review
- Reconstruction of the Global Neural Crest Gene Regulatory Network In Vivo.Developmental cell · 2019Article
- Insights into DDT Resistance from theGenetics · 2017Article
- Differential modulation of the cellular and humoral immune responses in Drosophila is mediated by the endosomal ARF1-Asrij axis.Scientific reports · 2017Article
- Examining cooperative binding of Sox2 on DC5 regulatory element upon complex formation with Pax6 through excess electron transfer assay.Nucleic acids research · 2016Article
- TRAP-rc, Translating Ribosome Affinity Purification from Rare Cell Populations of Drosophila Embryos.Journal of visualized experiments : JoVE · 2015Article
- Inhibitory activities of short linear motifs underlie Hox interactome specificity in vivo.eLife · 2015Article
- Genome-wide computational analysis reveals cardiomyocyte-specific transcriptional Cis-regulatory motifs that enable efficient cardiac gene therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2015Article
- Coordinated repression and activation of two transcriptional programs stabilizes cell fate during myogenesis.Development (Cambridge, England) · 2014Article
- Transcriptional regulation and alternative splicing cooperate in muscle fiber-type specification in flies and mammals.Experimental cell research · 2014Review
- Two enhancers control transcription of Drosophila muscleblind in the embryonic somatic musculature and in the central nervous system.PloS one · 2014Article
- Identification of pathways directly regulated by SHORT VEGETATIVE PHASE during vegetative and reproductive development in Arabidopsis.Genome biology · 2013Article
- Integrative analysis of the zinc finger transcription factor Lame duck in the Drosophila myogenic gene regulatory network.Proceedings of the National Academy of Sciences of the United States of America · 2012Article
- Differential regulation of mesodermal gene expression by Drosophila cell type-specific Forkhead transcription factors.Development (Cambridge, England) · 2012Article
- Tissue-specific analysis of chromatin state identifies temporal signatures of enhancer activity during embryonic development.Nature genetics · 2012Article
- Genome-wide transcription factor binding: beyond direct target regulation.Trends in genetics : TIG · 2011Review
- Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Understanding how complex patterns of temporal and spatial expression are regulated is central to deciphering genetic programs that drive development. Gene expression is initiated through the action of transcription factors and their cofactors converging on enhancer elements leading to a defined activity. Specific constellations of combinatorial occupancy are therefore often conceptualized as rigid binding codes that give rise to a common output of spatio-temporal expression. Here, we assessed this assumption using the regulatory input of two essential transcription factors within the Drosophila myogenic network. Mutations in either Myocyte enhancing factor 2 (Mef2) or the zinc-finger transcription factor lame duck (lmd) lead to very similar defects in myoblast fusion, yet the underlying molecular mechanism for this shared phenotype is not understood. Using a combination of ChIP-on-chip analysis and expression profiling of loss-of-function mutants, we obtained a global view of the regulatory input of both factors during development. The majority of Lmd-bound enhancers are co-bound by Mef2, representing a subset of Mef2's transcriptional input during these stages of development. Systematic analyses of the regulatory contribution of both factors demonstrate diverse regulatory roles, despite their co-occupancy of shared enhancer elements. These results indicate that Lmd is a tissue-specific modulator of Mef2 activity, acting as both a transcriptional activator and repressor, which has important implications for myogenesis. More generally, this study demonstrates considerable flexibility in the regulatory output of two factors, leading to additive, cooperative, and repressive modes of co-regulation.
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