Comparative genomic analysis reveals the evolutionary conservation of Pax gene family

Wang, Wei; Zhong, Jue; Wang, Yiquan

doi:10.1266/ggs.85.193

Cited by 19 publications

(17 citation statements)

References 36 publications

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“…It was also note that two sea squirt C. intestinalis genes CiCD36-a and CiCD36-b clustered with CD36 group in the phylogenetic tree, suggesting the typical CD36 genes were present in tunicates. This is consistent with the novel notion that tunicates closely related to vertebrates but not cephalochordates [34,40,41], although there are still some dispute about this [42].…”

Section: Discussionsupporting

confidence: 88%

Identification, evolution and expression of a CD36 homolog in the basal chordate amphioxus Branchiostoma japonicum

Zhang

et al. 2013

Fish & Shellfish Immunology

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Section: Discussionsupporting

confidence: 88%

Identification, evolution and expression of a CD36 homolog in the basal chordate amphioxus Branchiostoma japonicum

Zhang

et al. 2013

Fish & Shellfish Immunology

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“…NKX proteins are necessary for the proper development of motor neurons in the hindbrain (Pattyn et al 2003) and consistent with this role we see a significant enrichment (2.4, P-value = 0.005, Fisher's exact test) for NKX family TFBSs in our validated set of Hb enhancers. Similarly, the PAX gene family similarly comprises a large group of highly conserved TFs required for neuronal development (Wang et al 2010;Thompson and Ziman 2011). Furthermore, 10/30 validated predictions contained at least one PAX family motif (enrichment of 1.8 as compared with random genomic sequences with similar length and GC-content, P-value = 0.05, Fisher's exact test).…”

Section: Genome-wide Predictions Identify Novel Hindbrain Enhancersmentioning

confidence: 96%

Systematic elucidation and in vivo validation of sequences enriched in hindbrain transcriptional control

et al. 2012

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Illuminating the primary sequence encryption of enhancers is central to understanding the regulatory architecture of genomes. We have developed a machine learning approach to decipher motif patterns of hindbrain enhancers and identify 40,000 sequences in the human genome that we predict display regulatory control that includes the hindbrain. Consistent with their roles in hindbrain patterning, MEIS1, NKX6-1, as well as HOX and POU family binding motifs contributed strongly to this enhancer model. Predicted hindbrain enhancers are overrepresented at genes expressed in hindbrain and associated with nervous system development, and primarily reside in the areas of open chromatin. In addition, 77 (0.2%) of these predictions are identified as hindbrain enhancers on the VISTA Enhancer Browser, and 26,000 (60%) overlap enhancer marks (H3K4me1 or H3K27ac). To validate these putative hindbrain enhancers, we selected 55 elements distributed throughout our predictions and six low scoring controls for evaluation in a zebrafish transgenic assay. When assayed in mosaic transgenic embryos, 51/55 elements directed expression in the central nervous system. Furthermore, 30/34 (88%) predicted enhancers analyzed in stable zebrafish transgenic lines directed expression in the larval zebrafish hindbrain. Subsequent analysis of sequence fragments selected based upon motif clustering further confirmed the critical role of the motifs contributing to the classifier. Our results demonstrate the existence of a primary sequence code characteristic to hindbrain enhancers. This code can be accurately extracted using machine-learning approaches and applied successfully for de novo identification of hindbrain enhancers. This study represents a critical step toward the dissection of regulatory control in specific neuronal subtypes.[Supplemental material is available for this article.]In metazoans, precise spatiotemporal patterns of gene expression are modulated by the exquisite contributions of transcriptional regulatory sequences. These include enhancers that activate transcription in a manner frequently observed to be independent of distance, position, and orientation with respect to the promoter of their target genes (Banerji et al. 1981). Empirically validated enhancers are typically a few hundred base pairs long and comprise binding sites for multiple transcription factors (TFs). In turn, TFs bound to these sequences also interact with common co-activators, communicating with the basal transcription machinery assembled at the promoter, and increasing the rate of transcription (Bulger and Groudine 2011). Identifying the combinatorial protein-DNA and protein-protein interactions that determine spatial and temporal enhancer function is crucial to understanding how distinct cellular and developmental programs are established.The systematic discovery of enhancers has proven challenging, since they are often located at great genomic distances from the genes they regulate (Lettice et al. 2003). The classical approach to enhancer identification invo...

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“…Pax genes encode a family of highly conserved transcription factors characterized by the presence of a paired domain that confers sequence-specific binding to DNA; in addition, Pax transcription factors may also have an octapeptide motif and part or all of a homeobox DNA-binding domain (Balczarek et al, 1997; Chi and Epstein, 2002; Vorobyov and Horst, 2006; Lang et al, 2007; Wang et al, 2010). This family shows a high degree of evolutionary conservation throughout diverse lineages of metazoans, making it an ideal system to address relationships inside chordate phylum.…”

Section: Introductionmentioning

confidence: 99%

Conserved localization of Pax6 and Pax7 transcripts in the brain of representatives of sarcopterygian vertebrates during development supports homologous brain regionalization

et al. 2014

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Many of the genes involved in brain patterning during development are highly conserved in vertebrates and similarities in their expression patterns help to recognize homologous cell types or brain regions. Among these genes, Pax6 and Pax7 are expressed in regionally restricted patterns in the brain and are essential for its development. In the present immunohistochemical study we analyzed the distribution of Pax6 and Pax7 cells in the brain of six representative species of tetrapods and lungfishes, the closest living relatives of tetrapods, at several developmental stages. The distribution patterns of these transcription factors were largely comparable across species. In all species only Pax6 was expressed in the telencephalon, including the olfactory bulbs, septum, striatum, and amygdaloid complex. In the diencephalon, Pax6 and Pax7 were distinct in the alar and basal parts, mainly in prosomeres 1 and 3. Pax7 specifically labeled cells in the optic tectum (superior colliculus) and Pax6, but not Pax7, cells were found in the tegmentum. Pax6 was found in most granule cells of the cerebellum and Pax7 labeling was detected in cells of the ventricular zone of the rostral alar plate and in migrated cells in the basal plate, including the griseum centrale and the interpeduncular nucleus. Caudally, Pax6 cells formed a column, whereas the ventricular zone of the alar plate expressed Pax7. Since the observed Pax6 and Pax7 expression patterns are largely conserved they can be used to identify subdivisions in the brain across vertebrates that are not clearly discernible with classical techniques.

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Comparative genomic analysis reveals the evolutionary conservation of Pax gene family

Cited by 19 publications

References 36 publications

Identification, evolution and expression of a CD36 homolog in the basal chordate amphioxus Branchiostoma japonicum

Identification, evolution and expression of a CD36 homolog in the basal chordate amphioxus Branchiostoma japonicum

Systematic elucidation and in vivo validation of sequences enriched in hindbrain transcriptional control

Conserved localization of Pax6 and Pax7 transcripts in the brain of representatives of sarcopterygian vertebrates during development supports homologous brain regionalization

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