Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Transcription profiling of mouse control embryos and pbx2-MO;pbx4-MO embryos at 10 somites and at 18 somites.

ABSTRACT: Pbx homeodomain proteins have been implicated in the regulation of gene expression during muscle development. Whether Pbx proteins are required broadly for the regulation of muscle gene expression or are required for the expression of a specific subset of muscle gene expression is not known. We employed microarrays to determine the requirements for Pbx proteins during zebrafish development. Experiment Overall Design: Total RNA samples from control and pbx2-MO;pbx4-MO embryos were collected at two developmental stages: 10 somites and 18 somites. Their expression profiles were analyzed using Affymetrix zebrafish genome arrays, and the differentially hybridized genes were determined to be significant according to a FDR<0.05.

ORGANISM(S): Danio rerio

SUBMITTER: Yi Cao

PROVIDER: E-GEOD-8428 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Pbx homeodomain proteins direct Myod activity to promote fast-muscle differentiation.

Maves Lisa L Waskiewicz Andrew Jan AJ Paul Biswajit B Cao Yi Y Tyler Ashlee A Moens Cecilia B CB Tapscott Stephen J SJ

Development (Cambridge, England) 20070815 18

The basic helix-loop-helix (bHLH) transcription factor Myod directly regulates gene expression throughout the program of skeletal muscle differentiation. It is not known how a Myod-driven myogenic program is modulated to achieve muscle fiber-type-specific gene expression. Pbx homeodomain proteins mark promoters of a subset of Myod target genes, including myogenin (Myog); thus, Pbx proteins might modulate the program of myogenesis driven by Myod. By inhibiting Pbx function in zebrafish embryos, w ...[more]

PMID: 17699609

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Project description:The basic helix-loop-helix factor Myod initiates skeletal muscle differentiation by directly and sequentially activating sets of muscle differentiation genes, including those encoding muscle contractile proteins. We hypothesize that Pbx homeodomain proteins direct Myod to a subset of its transcriptional targets, in particular fast twitch muscle differentiation genes, thereby regulating the competence of muscle precursor cells to differentiate. We have previously shown that Pbx proteins bind with Myod on the promoter of the zebrafish fast muscle gene mylpfa and that Pbx proteins are required for Myod to activate mylpfa expression and the fast-twitch muscle-specific differentiation program in zebrafish embryos. Here we have investigated the interactions of Pbx with another muscle fiber-type regulator, Prdm1a, a SET-domain DNA-binding factor that directly represses mylpfa expression and fast muscle differentiation. The prdm1a mutant phenotype, early and increased fast muscle differentiation, is the opposite of the Pbx-null phenotype, delayed and reduced fast muscle differentiation. To determine whether Pbx and Prdm1a have opposing activities on a common set of genes, we used RNA-seq analysis to globally assess gene expression in zebrafish embryos with single- and double-losses-of-function for Pbx and Prdm1a. We find that the levels of expression of certain fast muscle genes are increased or approximately wild type in pbx2/4-MO;prdm1a-/- embryos, suggesting that Pbx activity normally counters the repressive action of Prdm1a for a subset of the fast muscle program. However, other fast muscle genes require Pbx but are not regulated by Prdm1a. Thus, our findings reveal that subsets of the fast muscle program are differentially regulated by Pbx and Prdm1a. Our findings provide an example of how Pbx homeodomain proteins act in a balance with other transcription factors to regulate subsets of a cellular differentiation program. Total RNA samples were genotyped and pooled for 4 sample types: control-MO;prdm1+/+; control-MO;prdm1-/-; pbx2/4-MO;prdm1+/+; and pbx2/4-MO;prdm1-/- embryos at the 10 somite (s) stage from three independent sets of egg collections/injections.

Dataset Information

Transcription profiling of mouse control embryos and pbx2-MO;pbx4-MO embryos at 10 somites and at 18 somites.

Publications

Pbx homeodomain proteins direct Myod activity to promote fast-muscle differentiation.

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