3D genome organization in the central nervous system, implications for neuropsychological disorders

Sun, Daijing; Jie, Weng; Dong, Yang; Jiang, Yan

doi:10.1016/j.jgg.2021.06.017

Cited by 7 publications

(4 citation statements)

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“…Finally, despite multiple studies attempting to study the spatial and temporal dynamics of brain chromatin spatial organization and their implications for gene regulation and relevance for disease [65,67,82], more data and more innovative methods to analyze such data are much needed for the better prioritization and pinpointing of relevant brain regions and developmental stages for brain-related disorders. With more studies examining diverse aspects of 3D genome organization in the brain and other components in the central nervous system (CNS) [32,[113][114][115][116], we anticipate novel discoveries for more comprehensively revealing the molecular etiology underlying brainand CNS-related disorders.…”

Section: Discussionmentioning

confidence: 99%

Understanding Regulatory Mechanisms of Brain Function and Disease through 3D Genome Organization

Liu

Zhong

Chen

et al. 2022

Genes

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The human genome has a complex and dynamic three-dimensional (3D) organization, which plays a critical role for gene regulation and genome function. The importance of 3D genome organization in brain development and function has been well characterized in a region- and cell-type-specific fashion. Recent technological advances in chromosome conformation capture (3C)-based techniques, imaging approaches, and ligation-free methods, along with computational methods to analyze the data generated, have revealed 3D genome features at different scales in the brain that contribute to our understanding of genetic mechanisms underlying neuropsychiatric diseases and other brain-related traits. In this review, we discuss how these advances aid in the genetic dissection of brain-related traits.

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Section: Discussionmentioning

confidence: 99%

Understanding Regulatory Mechanisms of Brain Function and Disease through 3D Genome Organization

Liu

Zhong

Chen

et al. 2022

Genes

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“…ncRNAs work both on the transcriptional and posttranscriptional level to affect the production and stability of mRNAs. In addition, the organization of the 3D genome, in which spatial interactions of chromatin help bring linearly distant genes and regulatory elements into proximity (such as enhancer-promoter loops), has emerged as a new epigenetic mechanism in recent years (Rajarajan et al, 2016;Sun et al, 2021). In the current Research Topic, we present seven articles exploring different aspects of epigenetics for multiple neuropsychiatric conditions (Figure 1).…”

Section: Neuroepigenetics Of Neuropsychiatric Disease-hope Success An...mentioning

confidence: 99%

Editorial: Neuroepigenetics of Neuropsychiatric Disease—Hope, Success and Obstacles for Translational Findings and Applications

2022

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“…Analogous to the influence of SINEs on gene expression, the absence of SETDB1 in neural precursor cells (NPCs) derepresses ERVs, impacting adjacent gene transcription [ 25 ], or serving as enhancer elements [ 18 ]. Beyond its role as an H3K9me3 ‘writer’, SETDB1 orchestrates 3D chromatin conformation within the brain [ 26 ]. Our previous study revealed its ability to maintain the topologically associating domain (TAD) conformation covering the protocadherin gene cluster, through H3K9me3 deposition, DNA methylation, and long-range repressive chromatin interactions [ 27 ].…”

Section: Introductionmentioning

confidence: 99%

SETDB1 regulates short interspersed nuclear elements and chromatin loop organization in mouse neural precursor cells

Sun,

Zhu,

Peng

et al. 2024

Genome Biol

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Background Transposable elements play a critical role in maintaining genome architecture during neurodevelopment. Short Interspersed Nuclear Elements (SINEs), a major subtype of transposable elements, are known to harbor binding sites for the CCCTC-binding factor (CTCF) and pivotal in orchestrating chromatin organization. However, the regulatory mechanisms controlling the activity of SINEs in the developing brain remains elusive. Results In our study, we conduct a comprehensive genome-wide epigenetic analysis in mouse neural precursor cells using ATAC-seq, ChIP-seq, whole genome bisulfite sequencing, in situ Hi-C, and RNA-seq. Our findings reveal that the SET domain bifurcated histone lysine methyltransferase 1 (SETDB1)-mediated H3K9me3, in conjunction with DNA methylation, restricts chromatin accessibility on a selective subset of SINEs in neural precursor cells. Mechanistically, loss of Setdb1 increases CTCF access to these SINE elements and contributes to chromatin loop reorganization. Moreover, de novo loop formation contributes to differential gene expression, including the dysregulation of genes enriched in mitotic pathways. This leads to the disruptions of cell proliferation in the embryonic brain after genetic ablation of Setdb1 both in vitro and in vivo. Conclusions In summary, our study sheds light on the epigenetic regulation of SINEs in mouse neural precursor cells, suggesting their role in maintaining chromatin organization and cell proliferation during neurodevelopment.

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3D genome organization in the central nervous system, implications for neuropsychological disorders

Cited by 7 publications

References 100 publications

Understanding Regulatory Mechanisms of Brain Function and Disease through 3D Genome Organization

Understanding Regulatory Mechanisms of Brain Function and Disease through 3D Genome Organization

Editorial: Neuroepigenetics of Neuropsychiatric Disease—Hope, Success and Obstacles for Translational Findings and Applications

SETDB1 regulates short interspersed nuclear elements and chromatin loop organization in mouse neural precursor cells

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