Leung Lab

@article{pmid38167730,

title = {Cell-type differential targeting of SETDB1 prevents aberrant CTCF binding, chromatin looping, and cis-regulatory interactions},

author = {Phoebe Lut Fei Tam and Ming Fung Cheung and Lu Yan Chan and Danny Leung},

doi = {10.1038/s41467-023-44578-0},

issn = {2041-1723},

year  = {2024},

date = {2024-01-01},

journal = {Nat Commun},

volume = {15},

number = {1},

pages = {15},

abstract = {SETDB1 is an essential histone methyltransferase that deposits histone H3 lysine 9 trimethylation (H3K9me3) to transcriptionally repress genes and repetitive elements. The function of differential H3K9me3 enrichment between cell-types remains unclear. Here, we demonstrate mutual exclusivity of H3K9me3 and CTCF across mouse tissues from different developmental timepoints. We analyze SETDB1 depleted cells and discover that H3K9me3 prevents aberrant CTCF binding independently of DNA methylation and H3K9me2. Such sites are enriched with SINE B2 retrotransposons. Moreover, analysis of higher-order genome architecture reveals that large chromatin structures including topologically associated domains and subnuclear compartments, remain intact in SETDB1 depleted cells. However, chromatin loops and local 3D interactions are disrupted, leading to transcriptional changes by modifying pre-existing chromatin landscapes. Specific genes with altered expression show differential interactions with dysregulated cis-regulatory elements. Collectively, we find that cell-type specific targets of SETDB1 maintain cellular identities by modulating CTCF binding, which shape nuclear architecture and transcriptomic networks.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid38003607,

title = {The Molecular Impacts of Retrotransposons in Development and Diseases},

author = {Phoebe Lut Fei Tam and Danny Leung},

doi = {10.3390/ijms242216418},

issn = {1422-0067},

year  = {2023},

date = {2023-11-01},

journal = {Int J Mol Sci},

volume = {24},

number = {22},

abstract = {Retrotransposons are invasive genetic elements that constitute substantial portions of mammalian genomes. They have the potential to influence nearby gene expression through their -regulatory sequences, reverse transcription machinery, and the ability to mold higher-order chromatin structures. Due to their multifaceted functions, it is crucial for host fitness to maintain strict regulation of these parasitic sequences to ensure proper growth and development. This review explores how subsets of retrotransposons have undergone evolutionary exaptation to enhance the complexity of mammalian genomes. It also highlights the significance of regulating these elements, drawing on recent studies conducted in human and murine systems.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37639608,

title = {Differential second messenger signaling via dopamine neurons bidirectionally regulates memory retention},

author = {Mai Takakura and Yu Hong Lam and Reiko Nakagawa and Man Yung Ng and Xinyue Hu and Priyanshu Bhargava and Abdalla G Alia and Yuzhe Gu and Zigao Wang and Takeshi Ota and Yoko Kimura and Nao Morimoto and Fumitaka Osakada and Ah Young Lee and Danny Leung and Tomoyuki Miyashita and Juan Du and Hiroyuki Okuno and Yukinori Hirano},

doi = {10.1073/pnas.2304851120},

issn = {1091-6490},

year  = {2023},

date = {2023-09-01},

journal = {Proc Natl Acad Sci U S A},

volume = {120},

number = {36},

pages = {e2304851120},

abstract = {Memory formation and forgetting unnecessary memory must be balanced for adaptive animal behavior. While cyclic AMP (cAMP) signaling via dopamine neurons induces memory formation, here we report that cyclic guanine monophosphate (cGMP) signaling via dopamine neurons launches forgetting of unconsolidated memory in . Genetic screening and proteomic analyses showed that neural activation induces the complex formation of a histone H3K9 demethylase, Kdm4B, and a GMP synthetase, Bur, which is necessary and sufficient for forgetting unconsolidated memory. Kdm4B/Bur is activated by phosphorylation through NO-dependent cGMP signaling via dopamine neurons, inducing gene expression, including  encoding a presynaptic protein. Accordingly, Kdm4B/Bur activation induced presynaptic changes. Our data demonstrate a link between cGMP signaling and synapses via gene expression in forgetting, suggesting that the opposing functions of memory are orchestrated by distinct signaling via dopamine neurons, which affects synaptic integrity and thus balances animal behavior.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Gao2023,

title = {Single-cell analysis reveals transcriptomic and epigenomic impacts on the maternal–fetal interface following SARS-CoV-2 infection},

author = {Lin Gao and Vrinda Mathur and Sabrina Ka Man Tam and Xuemeng Zhou and Ming Fung Cheung and Lu Yan Chan and Guadalupe Estrada-Gutiérrez and Bo Wah Leung and Sakita Moungmaithong and Chi Chiu Wang and Liona C. Poon and Danny Leung},

doi = {10.1038/s41556-023-01169-x},

issn = {14764679},

year  = {2023},

date = {2023-01-01},

journal = {Nature Cell Biology},

volume = {25},

issue = {7},

abstract = {During pregnancy the maternal–fetal interface plays vital roles in fetal development. Its disruption is frequently found in pregnancy complications. Recent studies show increased incidences of adverse pregnancy outcomes in patients with COVID-19; however, the mechanism remains unclear. Here we analysed the molecular impacts of SARS-CoV-2 infection on the maternal–fetal interface. Generating bulk and single-nucleus transcriptomic and epigenomic profiles from patients with COVID-19 and control samples, we discovered aberrant immune activation and angiogenesis patterns in distinct cells from patients. Surprisingly, retrotransposons were also dysregulated in specific cell types. Notably, reduced enhancer activities of LTR8B elements were functionally linked to the downregulation of pregnancy-specific glycoprotein genes in syncytiotrophoblasts. Our findings revealed that SARS-CoV-2 infection induced substantial changes to the epigenome and transcriptome at the maternal–fetal interface, which may be associated with pregnancy complications.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}