<i>Hox</i> Genes and Segmentation of the Hindbrain and Axial Skeleton

Alexander, Tara B.; Nolte, Christof; Krumlauf, Robb

doi:10.1146/annurev.cellbio.042308.113423

Cited by 271 publications

(292 citation statements)

References 151 publications

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“…Genes differentially expressed after cohesin cleavage do not correlate with cohesin; instead, a correlation with neighboring DNase hypersensitive sites marking potential regulatory elements suggests that these genes have lost contact to neighboring enhancers. Several misregulated genes belong to the developmentally important HOX clusters, whose properly timed and localized expression is regulated by topological domain organization and remote enhancers (22,23). In at least two HOX clusters (HOXA, HOXB) we observed a loss of interactions after cohesin cleavage (Fig.…”

Section: Discussionmentioning

confidence: 78%

“…4C). Hox genes have been shown to be regulated by antisense transcription as well as the topological organization of the locus and the contact to remote enhancers (22,23), but so far only for the HOXA cluster has a role cohesin and CTCF at the barrier element been shown (24). Among genes that are differentially expressed after CTCF depletion, we observed a clear enrichment of CTCF-binding at their promoters (Fig.…”

Section: Cohesin and Ctcf Depletion Affect Gene Expression In Differentmentioning

confidence: 72%

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Cohesin and CTCF differentially affect chromatin architecture and gene expression in human cells

Zuin

Dixon

Reijden

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

736

687

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Recent studies of genome-wide chromatin interactions have revealed that the human genome is partitioned into many selfassociating topological domains. The boundary sequences between domains are enriched for binding sites of CTCC-binding factor (CTCF) and the cohesin complex, implicating these two factors in the establishment or maintenance of topological domains. To determine the role of cohesin and CTCF in higher-order chromatin architecture in human cells, we depleted the cohesin complex or CTCF and examined the consequences of loss of these factors on higher-order chromatin organization, as well as the transcriptome. We observed a general loss of local chromatin interactions upon disruption of cohesin, but the topological domains remain intact. However, we found that depletion of CTCF not only reduced intradomain interactions but also increased interdomain interactions. Furthermore, distinct groups of genes become misregulated upon depletion of cohesin and CTCF. Taken together, these observations suggest that CTCF and cohesin contribute differentially to chromatin organization and gene regulation.Hi-C | transcriptional regulation | 4C | HOX cluster R ecent studies of the topological organization of the genome suggest that CTCC-binding factor (CTCF) and cohesin might be involved in establishment or maintenance of topological domains in the mammalian genome, as their binding sites are enriched at the boundaries of these domains (1). It was proposed that CTCF and cohesin might work together to facilitate longrange interactions in the genome (2). First, CTCF and the cohesin complex, consisting of the core subunits SMC3, SMC1, RAD21, and STAG1/SA1 or STAG2/SA2, were found to colocalize extensively throughout mammalian genomes (3-5). Second, both factors are involved in mediating long-range interactions (6-11). Finally, cohesin was shown to be important for CTCF's chromatin insulation function (3-5), whereas CTCF is necessary to recruit cohesin to the shared binding sites but not to chromatin (3). CTCF and cohesin have also been recently correlated with both interaction frequency and gene expression during differentiation (12), indicating that they may play major roles in mediating the impacts of chromatin structure on gene regulation. However, the exact mechanisms these factors use to contribute to chromatin structure and gene regulation are unclear, as depletion of these factors has not yet been systematically tested on a genome-wide basis. Whether the two factors work in concert or independently, through mechanisms, such as long-range enhancer looping (13) or chromatin insulation (2) to control chromatin structure and gene expression, is unknown. To determine the role of cohesin and CTCF in higher-order chromatin architecture in human cells, we depleted the cohesin complex or CTCF and examined the consequences of loss of these factors on domain structure and gene expression. Results Proteolytic Cleavage of RAD21 Leads to Loss of Long-Range ChromatinInteractions. To understand the contribution of cohesin to genom...

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Section: Discussionmentioning

confidence: 78%

Section: Cohesin and Ctcf Depletion Affect Gene Expression In Differentmentioning

confidence: 72%

Cohesin and CTCF differentially affect chromatin architecture and gene expression in human cells

Zuin

Dixon

Reijden

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

736

687

View full text Add to dashboard Cite

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“…The main discussion is set up using Drosophila and mouse as key experimental models, bringing in information from other systems where useful and possible. Owing to space limitations, we give priority to regulatory mechanisms other than classical transcriptional regulation, given that these have been well covered elsewhere (Alexander et al, 2009;Maeda and Karch, 2009;Tschopp and Duboule, 2011). This Review thus offers an account of the wide variety of molecular processes able to affect the regulation of Hox gene expression during animal development.…”

Section: Introductionmentioning

confidence: 99%

The regulation of Hox gene expression during animal development

2013

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Hox genes encode a family of transcriptional regulators that elicit distinct developmental programmes along the head-to-tail axis of animals. The specific regional functions of individual Hox genes largely reflect their restricted expression patterns, the disruption of which can lead to developmental defects and disease. Here, we examine the spectrum of molecular mechanisms controlling Hox gene expression in model vertebrates and invertebrates and find that a diverse range of mechanisms, including nuclear dynamics, RNA processing, microRNA and translational regulation, all concur to control Hox gene outputs. We propose that this complex multi-tiered regulation might contribute to the robustness of Hox expression during development.Wellcome Trust; Fundação para a Ciência e a Tecnologia grants

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“…Axial identity and boundaries of Hox gene expression are also set during somitogenesis (Alexander et al, 2009;Zákány et al, 2001). Mutations in the Notch pathway effector Rbpj were shown to disrupt the dynamic expression of Hoxd1 and Hoxd3, and, in transgenic mice with dominant negative alleles of Dll1 that have reduced Notch signaling in the PSM, there are homeotic vertebral transformations and subtle changes of Hox gene expression (Cordes et al, 2004).…”

Section: Evolution Of Genetic Pathways Regulating Somitogenesis In Rementioning

confidence: 99%

Reptile genomes open the frontier for comparative analysis of amniote development and regeneration

Tollis

Hutchins

Kusumi³

2014

Int. J. Dev. Biol.

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Developmental genetic studies of vertebrates have focused primarily on zebrafish, frog and mouse models, which have clear application to medicine and well-developed genomic resources. In contrast, reptiles represent the most diverse amniote group, but have only recently begun to gather the attention of genome sequencing efforts. Extant reptilian groups last shared a common ancestor ~280 million years ago and include lepidosaurs, turtles and crocodilians. This phylogenetic diversity is reflected in great morphological and behavioral diversity capturing the attention of biologists interested in mechanisms regulating developmental processes such as somitogenesis and spinal patterning, regeneration, the evolution of "snake-like" morphology, the formation of the unique turtle shell, and the convergent evolution of the four-chambered heart shared by mammals and archosaurs. The complete genome of the first non-avian reptile, the green anole lizard, was published in 2011 and has provided insights into the origin and evolution of amniotes. Since then, the genomes of multiple snakes, turtles, and crocodilians have also been completed. Here we will review the current diversity of available reptile genomes, with an emphasis on their evolutionary relationships, and will highlight how these genomes have and will continue to facilitate research in developmental and regenerative biology.

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Hox Genes and Segmentation of the Hindbrain and Axial Skeleton

Cited by 271 publications

References 151 publications

Cohesin and CTCF differentially affect chromatin architecture and gene expression in human cells

Cohesin and CTCF differentially affect chromatin architecture and gene expression in human cells

The regulation of Hox gene expression during animal development

Reptile genomes open the frontier for comparative analysis of amniote development and regeneration

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