QSER1 protects DNA methylation valleys from de novo methylation

Science, Год журнала: 2021, Номер 372(6538)

Опубликована: Апрель 9, 2021

DNA methylation is essential to mammalian development, and dysregulation can cause serious pathological conditions. Key enzymes responsible for deposition removal of are known, but how they cooperate regulate the landscape remains a central question. Using knockin reporter, we performed genome-wide CRISPR-Cas9 screen in human embryonic stem cells discover regulators. The top hit was an uncharacterized gene, QSER1, which proved be key guardian bivalent promoters poised enhancers developmental genes, especially those residing valleys (or canyons). We further demonstrate genetic biochemical interactions QSER1 TET1, supporting their cooperation safeguard transcriptional programs from DNMT3-mediated de novo methylation.

Язык: Английский

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A Structural Perspective on Readout of Epigenetic Histone and DNA Methylation Marks

Cold Spring Harbor Perspectives in Biology, Год журнала: 2016, Номер 8(3), С. a018754 - a018754

Опубликована: Март 1, 2016

Dinshaw J. Patel Structural Biology Department, Memorial Sloan-Kettering Cancer Center, New York, York 10065 Correspondence: pateld{at}mskcc.org

Язык: Английский

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From DNA damage to mutations: All roads lead to aging

Ageing Research Reviews, Год журнала: 2021, Номер 68, С. 101316 - 101316

Опубликована: Март 10, 2021

Язык: Английский

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Aberrant phase separation and cancer

FEBS Journal, Год журнала: 2021, Номер 289(1), С. 17 - 39

Опубликована: Фев. 14, 2021

Eukaryotic cells are intracellularly divided into numerous compartments or organelles, which coordinate specific molecules and biological reactions. Membrane‐bound organelles physically separated by lipid bilayers from the surrounding environment. Biomolecular condensates, also referred to membraneless micron‐scale cellular that lack membranous enclosures but function concentrate proteins RNA molecules, these involved in diverse processes. Liquid–liquid phase separation (LLPS) driven multivalent weak macromolecular interactions is a critical principle for formation of biomolecular multitude combinations among may drive liquid–liquid transition (LLPT). Dysregulation LLPS LLPT leads aberrant condensate amyloid formation, causes many human diseases, including neurodegeneration cancer. Here, we describe recent findings regarding abnormal forms condensates aggregation via cancer‐related cancer development mutation fusion genes. Moreover, discuss regulatory mechanisms occur drug candidates targeting mechanisms. Further understanding molecular events regulating how form tissue therapeutic strategies against tumorigenesis.

Язык: Английский

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p53 reactivation with induction of massive apoptosis-1 (PRIMA-1) inhibits amyloid aggregation of mutant p53 in cancer cells

Journal of Biological Chemistry, Год журнала: 2019, Номер 294(10), С. 3670 - 3682

Опубликована: Янв. 3, 2019

Язык: Английский

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