ArticleGenome research2008
Direct targets of the TRP63 transcription factor revealed by a combination of gene expression profiling and reverse engineering.
Article in Genome research, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed.
- NLRP10 maintains epidermal homeostasis by promoting keratinocyte survival and P63-dependent differentiation and barrier function.Cell death & disease · 2024Article
- ΔNp63α-mediated epigenetic regulation in keratinocyte senescence.Epigenetics · 2023Article
- Isoform-Specific Roles of Mutant p63 in Human Diseases.Cancers · 2021Review
- Master regulatory role of p63 in epidermal development and disease.Cellular and molecular life sciences : CMLS · 2018Review
- p63 exerts spatio-temporal control of palatal epithelial cell fate to prevent cleft palate.PLoS genetics · 2017Article
- TIGERi: modeling and visualizing the responses to perturbation of a transcription factor network.BMC bioinformatics · 2017Article
- Foxn1 regulates key target genes essential for T cell development in postnatal thymic epithelial cells.Nature immunology · 2016Article
- Understanding transcriptional regulatory networks using computational models.Current opinion in genetics & development · 2016Review
- Transcription factor p63 bookmarks and regulates dynamic enhancers during epidermal differentiation.EMBO reports · 2015Article
- A composite enhancer regulates p63 gene expression in epidermal morphogenesis and in keratinocyte differentiation by multiple mechanisms.Nucleic acids research · 2015Article
- Evaluating influence of microRNA in reconstructing gene regulatory networks.Cognitive neurodynamics · 2014Article
- Gene differential coexpression analysis based on biweight correlation and maximum clique.BMC bioinformatics · 2014Article
- CaSPIAN: a causal compressive sensing algorithm for discovering directed interactions in gene networks.PloS one · 2014Article
- Network based elucidation of drug response: from modulators to targets.BMC systems biology · 2013Review
- Reprogramming of lysosomal gene expression by interleukin-4 and Stat6.BMC genomics · 2013Article
- FGFR2 signaling underlies p63 oncogenic function in squamous cell carcinoma.The Journal of clinical investigation · 2013Article
- Insulin/IGF-1 controls epidermal morphogenesis via regulation of FoxO-mediated p63 inhibition.Developmental cell · 2013Article
- Incorporating time-delays in S-System model for reverse engineering genetic networks.BMC bioinformatics · 2013Article
- p63 control of desmosome gene expression and adhesion is compromised in AEC syndrome.Human molecular genetics · 2013Article
- Genome-wide analysis of p63 binding sites identifies AP-2 factors as co-regulators of epidermal differentiation.Nucleic acids research · 2012Article
Corrections and comments
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Authors and funding
6 authors.
Funding
Abstract
Genome-wide identification of bona-fide targets of transcription factors in mammalian cells is still a challenge. We present a novel integrated computational and experimental approach to identify direct targets of a transcription factor. This consists of measuring time-course (dynamic) gene expression profiles upon perturbation of the transcription factor under study, and in applying a novel "reverse-engineering" algorithm (TSNI) to rank genes according to their probability of being direct targets. Using primary keratinocytes as a model system, we identified novel transcriptional target genes of TRP63, a crucial regulator of skin development. TSNI-predicted TRP63 target genes were validated by Trp63 knockdown and by ChIP-chip to identify TRP63-bound regions in vivo. Our study revealed that short sampling times, in the order of minutes, are needed to capture the dynamics of gene expression in mammalian cells. We show that TRP63 transiently regulates a subset of its direct targets, thus highlighting the importance of considering temporal dynamics when identifying transcriptional targets. Using this approach, we uncovered a previously unsuspected transient regulation of the AP-1 complex by TRP63 through direct regulation of a subset of AP-1 components. The integrated experimental and computational approach described here is readily applicable to other transcription factors in mammalian systems and is complementary to genome-wide identification of transcription-factor binding sites.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.