Serial Inversions Induce Tissue-specific Architectural Stripes, Gene Misexpression and Congenital Malformations
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PROVIDER: PRJNA480261 | ENA |
REPOSITORIES: ENA
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Project description:Here we study the effect of balanced chromosomal rearrangements (BCRs) on gene expression in vivo in mouse embryos by generating a series of genomic inversions that place an active enhancer cluster located in the Epha4 regulatory domain at different positions within a neighboring gene dense region. Expression studies in embryonic limb buds show that the inverted enhancer cluster was able to activate several genes downstream of its new position, resulting in gene misexpression and limb phenotypes. Capture Hi-C from mutant limb buds showed that the activated genes were located within a region of asymmetric three-dimensional contacts, so called architectural stripes. Deletion of the CTCF binding site at that position of the stripe anchor resulted in a collapse of the stripes, down regulation of ectopic gene expression, and a rescue of the skeletal phenotype. In cells in which the enhancers are not active, such as mouse embryonic stem cells (mESCs), stripes do not form, indicating that their formation is also dependent on enhancer activity. Based on HiC from limb buds we show that architectural stripes are a frequent feature in the genome often associated with developmentally active enhancers. Thus, BCRs can induce ectopic gene expression via the formation of asymmetric chromatin contacts. The formation of these stripes is dependent on CTCF anchors and enhancer activity.
2018-11-19 | GSE116793 | GEO
Project description:Here we study the effect of balanced chromosomal rearrangements (BCRs) on gene expression in vivo in mouse embryos by generating a series of genomic inversions that place an active enhancer cluster located in the Epha4 regulatory domain at different positions within a neighboring gene dense region. Expression studies in embryonic limb buds show that the inverted enhancer cluster was able to activate several genes downstream of its new position, resulting in gene misexpression and limb phenotypes. Capture Hi-C from mutant limb buds showed that the activated genes were located within a region of asymmetric three-dimensional contacts, so called architectural stripes. Deletion of the CTCF binding site at that position of the stripe anchor resulted in a collapse of the stripes, down regulation of ectopic gene expression, and a rescue of the skeletal phenotype. In cells in which the enhancers are not active, such as mouse embryonic stem cells (mESCs), stripes do not form, indicating that their formation is also dependent on enhancer activity. Based on HiC from limb buds we show that architectural stripes are a frequent feature in the genome often associated with developmentally active enhancers. Thus, BCRs can induce ectopic gene expression via the formation of asymmetric chromatin contacts. The formation of these stripes is dependent on CTCF anchors and enhancer activity.
2018-11-19 | GSE116792 | GEO
Project description:Here we study the effect of balanced chromosomal rearrangements (BCRs) on gene expression in vivo in mouse embryos by generating a series of genomic inversions that place an active enhancer cluster located in the Epha4 regulatory domain at different positions within a neighboring gene dense region. Expression studies in embryonic limb buds show that the inverted enhancer cluster was able to activate several genes downstream of its new position, resulting in gene misexpression and limb phenotypes. Capture Hi-C from mutant limb buds showed that the activated genes were located within a region of asymmetric three-dimensional contacts, so called architectural stripes. Deletion of the CTCF binding site at that position of the stripe anchor resulted in a collapse of the stripes, down regulation of ectopic gene expression, and a rescue of the skeletal phenotype. In cells in which the enhancers are not active, such as mouse embryonic stem cells (mESCs), stripes do not form, indicating that their formation is also dependent on enhancer activity. Based on HiC from limb buds we show that architectural stripes are a frequent feature in the genome often associated with developmentally active enhancers. Thus, BCRs can induce ectopic gene expression via the formation of asymmetric chromatin contacts. The formation of these stripes is dependent on CTCF anchors and enhancer activity.
2018-11-19 | GSE116791 | GEO
Project description:Here we study the effect of balanced chromosomal rearrangements (BCRs) on gene expression in vivo in mouse embryos by generating a series of genomic inversions that place an active enhancer cluster located in the Epha4 regulatory domain at different positions within a neighboring gene dense region. Expression studies in embryonic limb buds show that the inverted enhancer cluster was able to activate several genes downstream of its new position, resulting in gene misexpression and limb phenotypes. Capture Hi-C from mutant limb buds showed that the activated genes were located within a region of asymmetric three-dimensional contacts, so called architectural stripes. Deletion of the CTCF binding site at that position of the stripe anchor resulted in a collapse of the stripes, down regulation of ectopic gene expression, and a rescue of the skeletal phenotype. In cells in which the enhancers are not active, such as mouse embryonic stem cells (mESCs), stripes do not form, indicating that their formation is also dependent on enhancer activity. Based on HiC from limb buds we show that architectural stripes are a frequent feature in the genome often associated with developmentally active enhancers. Thus, BCRs can induce ectopic gene expression via the formation of asymmetric chromatin contacts. The formation of these stripes is dependent on CTCF anchors and enhancer activity.
2018-11-19 | GSE116790 | GEO
Project description:Serial Inversions Induce Tissue-specific Architectural Stripes, Gene Misexpression and Congenital Malformations [ChIP-seq]
| PRJNA480256 | ENA
Project description:Serial Inversions Induce Tissue-specific Architectural Stripes, Gene Misexpression and Congenital Malformations [cHi-C]
| PRJNA480257 | ENA
Project description:Serial Inversions Induce Tissue-specific Architectural Stripes, Gene Misexpression and Congenital Malformations [Hi-C]
| PRJNA480258 | ENA
Project description:Serial Inversions Induce Tissue-specific Architectural Stripes, Gene Misexpression and Congenital Malformations [RNA-Seq]
| PRJNA480259 | ENA
Project description:This SuperSeries is composed of the SubSeries listed below.
2018-11-19 | GSE116794 | GEO
Project description:Changes in gene regulation rapidly accumulate between species and may contribute to reproductive isolation through misexpression of genes in interspecific hybrids. Hybrid misexpression, defined by expression levels outside the range of both parental species, is thought to be a result of cis- and trans-acting regulatory changes that interact in the hybrid, or arise from changes in the relative abundance of various tissues or cell types due to defects in developmental. Here, we show that misexpressed genes in a sterile interspecific Saccharomyces yeast hybrid result from a heterochronic shift in the timing of the normal meiotic gene expression program. By tracking nuclear divisions, we find that S. cerevisiae initiates meiosis earlier than its closest known relative, S. paradoxus, yet both species complete meiosis at the same time. Although the hybrid up- and down-regulates genes in a similar manner to both parents, the hybrid meiotic program occurs earlier than both parents. The timing shift results in a heterochronic pattern of misexpression throughout meiosis I and the beginning of meiosis II. Coincident with the timing of misexpression, we find an increase in the relative abundance of opposing cis and trans-acting changes and compensatory changes, as well as a transition from predominantly trans-acting to cis-acting expression divergence over the course of meiosis. However, misexpression does not appear to be a direct consequence of cis- and trans-acting regulatory divergence. Our results demonstrate that hybrid misexpression in yeast results from a heterochronic shift in the meiotic gene expression program. We analyzed three biological replicates of the parental yeast strains, S. cerevisiae and S. paradoxus, and four replicates of their hybrid over four developmental time points. Two hybrid replicates contain MATa from S. cerevisiae and MATalpha from S. paradoxus. The other two hybrid replicates are reciprocal crosses. The developmental time points are T0, which serves as a control, and is the moment cells enter sporulation media. M1 is the beginning of meiosis I. M1/M2 is the overlap of the end of meiosis I and the beginning of meiosis II. M2 is the end of meiosis II.
2013-10-31 | E-GEOD-51809 | biostudies-arrayexpress