Deep conservation of the enhancer regulatory code in animals

Interactions of transcription factors (TFs) with DNA regulatory sequences, known as enhancers, specify cell identity during animal development. Unlike TFs, the origin and evolution of enhancers has been difficult to trace. We drove zebrafish and mouse developmental transcription using enhancers from an evolutionarily distant marine sponge. Some of these sponge enhancers are located in highly conserved microsyntenic regions, including an Islet enhancer in the Islet-Scaper region. We found that Islet enhancers in humans and mice share a suite of TF binding motifs with sponges, and that they drive gene expression patterns similar to those of sponge and endogenous Islet enhancers in zebrafish. Our results suggest the existence of an ancient and conserved, yet flexible, genomic regulatory syntax that has been repeatedly co-opted into cell type–specific gene regulatory networks across the animal kingdom.

Selective Coregulator Function and Restriction of Steroid Receptor Chromatin Occupancy by Hic-5

Steroid receptors (SRs) bind specific DNA regulatory sequences, thereby activating and repressing gene expression. We previously showed that transcriptional coregulator Hic-5 facilitates glucocorticoid regulation of some genes but blocks glucocorticoid regulation of others. Here, in a genome-wide analysis, Hic-5 depletion dramatically increased the global number of sites occupied by glucocorticoid receptor (GR) α (the major GR isoform), and many binding sites blocked by Hic-5 were associated with genes for which Hic-5 also blocked glucocorticoid-regulated expression. Hic-5 had similar effects on GRγ (a splice variant of GRα) and estrogen receptor α (ERα), facilitating hormonal regulation of some genes and blocking hormonal regulation of others. As with GRα, Hic-5 blocking of hormonal gene regulation mediated by GRγ and ERα was associated with blocking of GRγ and ERα occupancy at nearby sites. Hic-5 supported hormonal regulation of many more genes for GRα than for GRγ or ERα and thus exhibited selective coregulator functions for different SRs. In contrast, the number of Hic-5–blocked genes was similar for all 3 SRs. In addition to classic coregulator activity, Hic-5 influences the genomic occupancy of multiple SRs and thereby blocks some aspects of hormonal regulation. Thus, Hic-5, because of its tissue-specific expression, could contribute to tissue-specific genomic occupancy and gene regulation by SRs.

Characterization of Putativecis-Regulatory Elements in Genes Preferentially Expressed inArabidopsisMale Meiocytes

Meiosis is essential for plant reproduction because it is the process during which homologous chromosome pairing, synapsis, and meiotic recombination occur. The meiotic transcriptome is difficult to investigate because of the size of meiocytes and the confines of anther lobes. The recent development of isolation techniques has enabled the characterization of transcriptional profiles in male meiocytes ofArabidopsis. Gene expression in male meiocytes shows unique features. The direct interaction of transcription factors (TFs) with DNA regulatory sequences forms the basis for the specificity of transcriptional regulation. Here, we identified putativecis-regulatory elements (CREs) associated with male meiocyte-expressed genes usingin silicotools. The upstream regions (1 kb) of the top 50 genes preferentially expressed inArabidopsismeiocytes possessed conserved motifs. These motifs are putative binding sites of TFs, some of which share common functions, such as roles in cell division. In combination with cell-type-specific analysis, our findings could be a substantial aid for the identification and experimental verification of the protein-DNA interactions for the specific TFs that drive gene expression in meiocytes.

Molecular Basis of Skeletal Muscle Regeneration

Skeletal muscle regeneration is a vital process with important implications for various muscle myopathies and adaptations to physiological overload. Few of the molecular regulatory proteins controlling this process have so far been identified. Several growth factors have defined effects on myogenic precursor cells and appear to also be involved during regeneration. In addition, factors that may be released by cells of the immune system may activate satellite cells during regeneration. Many of these growth factors are associated with signalling cascades which transmit information to the nucleus. The nuclear "receptors" that receive the incoming signals are transcription factors that interact with DNA regulatory sequences in order to modulate gene expression. Of the nuclear factors isolated so far, the immediate-early genes are associated with muscle precursor cell proliferation. This review aims to synthesize the extensive research on myogenic differentiation and relate this to research concerning the molecular regulation of skeletal muscle regeneration. Key words: satellite cells, growth factors, signal transduction, transcription factors, gene regulation, overload adaptation