Three-dimensional Genome Organization Maps in Normal Haematopoietic Stem Cells and Acute Myeloid Leukemia

Wang, Benny; Kong, Lingshi; Babu, Deepak; Choudhary, Ruchi; Fam, Winnie; Tng, Jia Qi; Goh, Yufen; Liu, Xin; Song, Fang Fang; Chia, Priscella Shirley; Chan, Ming Chun; An, Ömer; Tham, Cheng Yong; Benoukraf, Touati; Yang, Henry; Wang, Wilson; Chng, Wee Joo; Tenen, Daniel G.; Fullwood, Melissa J.

doi:10.1101/2020.04.18.047738

Cited by 3 publications

(3 citation statements)

References 43 publications

(52 reference statements)

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“…Loop calls from in-situ Hi-C experiments on HAP1 cells were obtained from [40]. Loop and TAD calls from in-situ Hi-C experiments on HSC samples were obtained from [45]. Loop calls from additional Hi-C experiments on HSC samples were obtained from [46].…”

Section: Methodsmentioning

confidence: 99%

Widespread contribution of transposable elements to the rewiring of mammalian 3D genomes and gene regulation

Choudhary

Quaid

Schmidt

et al. 2022

Preprint

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Transposable elements (TEs) are major contributors of genetic material in mammalian genomes. These often include binding sites for architectural proteins, including the multifarious master protein, CTCF. These TE-derived architectural protein binding sites shape the 3D genome by creating loops, domains, and compartments borders as well as RNA-DNA chromatin interactions, all of which play a role in the compact packaging of DNA in the nucleus and have the potential to facilitate regulatory function.In this study, we explore the widespread contribution of TEs to mammalian 3D genomes by quantifying the extent to which they give rise to loops and domain border differences across various cell types and species using a variety of 3D genome mapping technologies. We show that specific (sub-)families of TEs have significantly contributed to lineage-specific 3D chromatin structures in specific mammals. In many cases, these loops have the potential to facilitate interaction between distant cis-regulatory elements and target genes, and domains have the potential to segregate chromatin state to impact gene expression in a lineage-specific and cell-type-specific manner. Backing our extensive conformation study cataloguing and computational analyses, we perform experimental validation using CRISPR-Cas9 to delete one such candidate TE and show disruption of species-specific 3D chromatin structure.Taken together, we comprehensively quantify and selectively validate our finding that TEs contribute significantly to 3D genome organization and continuously shape it to affect gene regulation during the course of mammalian evolution over deep time.

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Section: Methodsmentioning

confidence: 99%

Widespread contribution of transposable elements to the rewiring of mammalian 3D genomes and gene regulation

Choudhary

Quaid

Schmidt

et al. 2022

Preprint

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show abstract

“…Loop and TAD calls from in-situ Hi-C experiments on HSC samples were obtained from ref. 51 . Loop calls from additional Hi-C experiments on HSC samples were obtained from ref.…”

Section: Dataset Geo Accession Numbersmentioning

confidence: 99%

“…generated in this study have been deposited in the Gene Expression Omnibus (GEO) database under accession code GSE222526. Publicly available sequencing datasets analyzed in this study include loop data that can be found in the supplementary information of 51 . H3K4me2 ChIA-PET can be accessed from GSE32677.…”

Section: Atac-seq Experimentsmentioning

confidence: 99%

Widespread contribution of transposable elements to the rewiring of mammalian 3D genomes

et al. 2023

View full text Add to dashboard Cite

Transposable elements (TEs) are major contributors of genetic material in mammalian genomes. These often include binding sites for architectural proteins, including the multifarious master protein, CTCF, which shapes the 3D genome by creating loops, domains, compartment borders, and RNA-DNA interactions. These play a role in the compact packaging of DNA and have the potential to facilitate regulatory function. In this study, we explore the widespread contribution of TEs to mammalian 3D genomes by quantifying the extent to which they give rise to loops and domain border differences across various cell types and species using several 3D genome mapping technologies. We show that specific families and subfamilies of TEs have contributed to lineage-specific 3D chromatin structures across mammalian species. In many cases, these loops may facilitate sustained interaction between distant cis-regulatory elements and target genes, and domains may segregate chromatin state to impact gene expression in a lineage-specific manner. An experimental validation of our analytical findings using CRISPR-Cas9 to delete a candidate TE resulted in disruption of species-specific 3D chromatin structure. Taken together, we comprehensively quantify and selectively validate our finding that TEs contribute to shaping 3D genome organization and may, in some cases, impact gene regulation during the course of mammalian evolution.

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3D chromatin architecture and epigenetic regulation in cancer stem cells

Feng

Pauklin

2021

Protein Cell

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Dedifferentiation of cell identity to a progenitor-like or stem cell-like state with increased cellular plasticity is frequently observed in cancer formation. During this process, a subpopulation of cells in tumours acquires a stem cell-like state partially resembling to naturally occurring pluripotent stem cells that are temporarily present during early embryogenesis. Such characteristics allow these cancer stem cells (CSCs) to give rise to the whole tumour with its entire cellular heterogeneity and thereby support metastases formation while being resistant to current cancer therapeutics. Cancer development and progression are demarcated by transcriptional dysregulation. In this article, we explore the epigenetic mechanisms shaping gene expression during tumorigenesis and cancer stem cell formation, with an emphasis on 3D chromatin architecture. Comparing the pluripotent stem cell state and epigenetic reprogramming to dedifferentiation in cellular transformation provides intriguing insight to chromatin dynamics. We suggest that the 3D chromatin architecture could be used as a target for re-sensitizing cancer stem cells to therapeutics.

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Three-dimensional Genome Organization Maps in Normal Haematopoietic Stem Cells and Acute Myeloid Leukemia

Cited by 3 publications

References 43 publications

Widespread contribution of transposable elements to the rewiring of mammalian 3D genomes and gene regulation

Widespread contribution of transposable elements to the rewiring of mammalian 3D genomes and gene regulation

Widespread contribution of transposable elements to the rewiring of mammalian 3D genomes

3D chromatin architecture and epigenetic regulation in cancer stem cells

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