
@article {152152,
	title = {NSD3 protein methylation and stabilization transforms human ES cells into variant state.},
	journal = {Life Sci Alliance},
	volume = {8},
	year = {2025},
	month = {2025 Mar},
	abstract = {<p>Cultured human embryonic stem cells (hESCs) can develop genetic anomalies that increase their susceptibility to transformation. In this study, we characterized a variant hESC (vhESC) line and investigated the molecular mechanisms leading to the drift towards a transformed state. Our findings revealed that vhESCs up-regulate EMT-specific markers, accelerate wound healing, exhibit compromised lineage differentiation, and retain pluripotency gene expression in teratomas. Furthermore, we discovered an altered epigenomic landscape and overexpression of the lysine methyltransferases EHMT1, EHMT2, and NSD group of proteins in vhESCs. Remarkably, depleting NSD3 oncogene reversed the molecular and phenotypic changes in vhESCs. We identified a detailed mechanism where EHMT2 interacts and methylates NSD3 at lysine 477, stabilizing its protein levels in vhESCs. In addition, we showed that NSD3 levels are regulated by protein degradation in hESCs, and its stabilization leads to the emergence of the variant state. Overall, our study identify that misregulation of NSD3 in pluripotent stem cells, through methylation-mediated abrogation of its protein degradation, drives hESCs towards oncogenic transformation.</p>
},
	keywords = {Cell Differentiation, Cell Line, Cell Transformation, Neoplastic, Epigenesis, Genetic, Epithelial-Mesenchymal Transition, Histone-Lysine N-Methyltransferase, Human Embryonic Stem Cells, Humans, Intracellular Signaling Peptides and Proteins, Methylation, Nuclear Proteins, Pluripotent Stem Cells, Protein Stability, Repressor Proteins},
	issn = {2575-1077},
	doi = {10.26508/lsa.202402871},
	author = {Krishnamoorthy, Vignesh K and Hamdani, Fariha and Shukla, Pooja and Rao, Radhika Arasala and Anaitullah, Shaikh and Biligiri, Kriti Kestur and Kadumuri, Rajashekar Varma and Pothula, Purushotham Reddy and Chavali, Sreenivas and Rampalli, Shravanti}
}
@article {117962,
	title = {Initiation of wound healing is regulated by the convergence of mechanical and epigenetic cues.},
	journal = {PLoS Biol},
	volume = {20},
	year = {2022},
	month = {2022 Sep},
	pages = {e3001777},
	abstract = {<p>Wound healing in the skin is a complex physiological process that is a product of a cell state transition from homeostasis to repair. Mechanical cues are increasingly being recognized as important regulators of cellular reprogramming, but the mechanism by which it is translated to changes in gene expression and ultimately cellular behavior remains largely a mystery. To probe the molecular underpinnings of this phenomenon further, we used the down-regulation of caspase-8 as a biomarker of a cell entering the wound healing program. We found that the wound-induced release of tension within the epidermis leads to the alteration of gene expression via the nuclear translocation of the DNA methyltransferase 3A (DNMT3a). This enzyme then methylates promoters of genes that are known to be down-regulated in response to wound stimuli as well as potentially novel players in the repair program. Overall, these findings illuminate the convergence of mechanical and epigenetic signaling modules that are important regulators of the transcriptome landscape required to initiate the tissue repair process in the differentiated layers of the epidermis.</p>
},
	keywords = {Biomarkers, Caspase 8, Cues, Epigenesis, Genetic, Wound Healing},
	issn = {1545-7885},
	doi = {10.1371/journal.pbio.3001777},
	author = {Bhatt, Tanay and Dey, Rakesh and Hegde, Akshay and Ketkar, Alhad Ashok and Pulianmackal, Ajai J and Deb, Ashim P and Rampalli, Shravanti and Jamora, Colin}
}
