The Three-Dimensional Organization of Mammalian Genomes

Yu, Miao; Ren, Bing

doi:10.1146/annurev-cellbio-100616-060531

Cited by 332 publications

(294 citation statements)

References 138 publications

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“…There is evidence that TAD boundaries act as genetic insulators, ensuring appropriate enhancerpromoter interactions (Dixon et al 2012;Krivega & Dean 2017). Disruption of TAD boundaries can lead to increased interactions between TADs, resulting in an altered phenotype (Yu & Ren 2017;Furlong & Levine 2018).…”

Section: Candidate Genesmentioning

confidence: 99%

Understanding the effects of the bovine POLLED variants

Aldersey

Sonstegard²,

Williams

et al. 2020

Animal Genetics

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Summary Horns are paired appendages on the head of bovine species, comprising an inner bony core and outer keratin sheath. The horn bud forms during early fetal development but ossification of the developing horn does not occur until approximately 1 month after birth. Little is known about the genetic pathways that lead to horn growth. Hornless, or polled, animals are found in all domestic bovids. Histological studies of bovine fetuses have shown that the horn bud does not form in polled individuals. There are currently four known genetic variants for polledness in cattle on BTA1. All of the variants are intergenic, but probably affect regulation of nearby genes or long non‐coding RNAs. Transcriptomic studies suggest that the expression of two nearby long non‐coding RNAs are affected by the Celtic POLLED variant, but further studies are required to confirm these data. Candidate genes located elsewhere in the genome are involved in regulating bone formation and epithelial‐to‐mesenchymal transition. Expression of one of these candidate genes, RXFP2, appears to be reduced in the fetal horn bud of polled animals carrying the Celtic variant compared with horned individuals. Investigating horn ontogenesis and the genetic pathway by which the POLLED variants prevent horn development has implications for cattle breeding. If the genetic basis of horn bud formation and polledness is better understood, then new targets may be identified for precision genome editing to create polled individuals.

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Section: Candidate Genesmentioning

confidence: 99%

Understanding the effects of the bovine POLLED variants

Aldersey

Sonstegard²,

Williams

et al. 2020

Animal Genetics

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“…The 3D spatial organization of the chromosomes in the nucleus of eukaryotic cells appears to be cell type specific [1][2][3][4][5][6][7]. What determines this cell type specific organization and how that organization relates to patterns of gene expression remain crucial questions in structural genomics.…”

Section: Introductionmentioning

confidence: 99%

Exploring Chromosomal Structural Heterogeneity Across Multiple Cell Lines

Cheng

Contessoto

Aiden

et al. 2020

Preprint

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“…The relationship between transcription and the 3D chromatin structures is one of the most fundamental questions in the post-genomic era [1][2][3][4]. Mounting evidence has shown that transcription activities correlate with more DNA interactions in development and diseases [5][6][7][8].…”

Section: Introductionmentioning

confidence: 99%

Genome-wide analyses of chromatin interactions after the loss of Pol I, Pol II and Pol III

Jiang

Huang

lun

et al. 2020

Preprint

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Background:The relationship between transcription and the 3D genome organization is one of the most important questions in molecular biology, but the roles of transcription in 3D chromatin remain controversial. Multiple groups showed that transcription affects global Cohesin binding and genome 3D structures. At the same time, several studies have indicated that transcription inhibition does not affect global chromatin interactions.Results: Here, we provide the most comprehensive evidence to date to demonstrate that transcription plays a marginal role in organizing the 3D genome in mammalian cells: 1) degraded Pol I, Pol II and Pol III proteins in mESCs, and showed their loss results in little or no changes of global 3D chromatin structures for the first time; 2) selected RNA polymerases high abundance binding sitesassociated interactions and found they still persist after the degradation; 3) generated higher resolution chromatin interaction maps and revealed that transcription inhibition mildly alters small loop domains; 4) identified Pol II bound but CTCF and Cohesin unbound loops and disclosed that they are largely resistant to transcription inhibition. Interestingly, Pol II depletion for a longer time significantly affects the chromatin accessibility and Cohesin occupancy, suggesting RNA polymerases are capable of affecting the 3D genome indirectly.So, the direct and indirect effects of transcription inhibition explain the previous confusing effects on the 3D genome. Conclusions:We conclude that Pol I, Pol II, and Pol III loss only mildly alter chromatin interactions in mammalian cells, suggesting the 3D chromatin structures are pre-established and relatively stable.

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The Three-Dimensional Organization of Mammalian Genomes

Cited by 332 publications

References 138 publications

Understanding the effects of the bovine POLLED variants

Understanding the effects of the bovine POLLED variants

Exploring Chromosomal Structural Heterogeneity Across Multiple Cell Lines

Genome-wide analyses of chromatin interactions after the loss of Pol I, Pol II and Pol III

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