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Genomic and computational approaches to dissect the mechanisms of STAT3's universal and cell type-specific functions.

ABSTRACT: STAT3 is the quintessential pleiotropic transcription factor with many biological roles throughout development as well as in multiple adult tissues. Its functional heterogeneity is encoded in the range of genome-wide binding patterns that specify different regulatory networks in distinct cell types. However, STAT3 does not display remarkable DNA binding preferences that may help correlate specific motifs with individual biological functions or cell types. Therefore, achieving a detailed understanding of the regulatory mechanisms that endow STAT3 (or any other pleiotropic transcription factor) with such a rainbow of functions is not only a central problem in biology but also a fiendishly difficult one. Here we describe key genomic and computational approaches that have shed light into this question, and present the two current models of STAT3 binding (universal and cell type-specific). We also discuss the role that the local epigenetic environment plays in the selection of STAT3 binding sites.

SUBMITTER: Hutchins AP

PROVIDER: S-EPMC3876425 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature

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Genomic and computational approaches to dissect the mechanisms of STAT3's universal and cell type-specific functions.

Hutchins Andrew Paul AP Diez Diego D Miranda-Saavedra Diego D

JAK-STAT 20130520 4

STAT3 is the quintessential pleiotropic transcription factor with many biological roles throughout development as well as in multiple adult tissues. Its functional heterogeneity is encoded in the range of genome-wide binding patterns that specify different regulatory networks in distinct cell types. However, STAT3 does not display remarkable DNA binding preferences that may help correlate specific motifs with individual biological functions or cell types. Therefore, achieving a detailed understa ...[more]

PMID: 24416643

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Project description:BackgroundNAC domain transcription factors are important transcriptional regulators involved in plant growth, development and stress responses. Recent studies have revealed several classes of NAC transcriptional factors crucial for controlling secondary cell wall biosynthesis. These transcriptional factors mainly include three classes, SND, NST and VND. Despite progress, most current analysis is carried out in the model plant Arabidopsis. Moreover, many downstream genes regulated by these transcriptional factors are still not clear.MethodsIn order to identify the key homologue genes across species and discover the network controlling cell wall biosynthesis, we carried out comparative genome analysis of NST, VND and SND genes across 19 higher plant species along with computational modelling of genes regulated or co-regulated with these transcriptional factors.ResultsThe comparative genome analysis revealed that evolutionarily the secondary-wall-associated NAC domain transcription factors first appeared in Selaginella moellendorffii. In fact, among the three groups, only VND genes appeared in S. moellendorffii, which is evolutionarily earlier than the other two groups. The Arabidopsis and rice gene expression analysis showed specific patterns of the secondary cell wall-associated NAC genes (SND, NST and VND). Most of them were preferentially expressed in the stem, especially the second internodes. Furthermore, comprehensive co-regulatory network analysis revealed that the SND and MYB genes were co-regulated, which indicated the coordinative function of these transcriptional factors in modulating cell wall biosynthesis. In addition, the co-regulatory network analysis revealed many novel genes and pathways that could be involved in cell wall biosynthesis and its regulation. The gene ontology analysis also indicated that processes like carbohydrate synthesis, transport and stress response, are coordinately regulated toward cell wall biosynthesis.ConclusionsOverall, we provided a new insight into the evolution and the gene regulatory network of a subgroup of the NAC gene family controlling cell wall composition through bioinformatics data mining and bench validation. Our work might benefit to elucidate the possible molecular mechanism underlying the regulation network of secondary cell wall biosynthesis.

Dataset Information

Genomic and computational approaches to dissect the mechanisms of STAT3's universal and cell type-specific functions.

Publications

Genomic and computational approaches to dissect the mechanisms of STAT3's universal and cell type-specific functions.

Similar Datasets

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