A5100323333- Epigenetics and DNA Methylation
- Cancer-related gene regulation
- DNA Repair Mechanisms
- RNA modifications and cancer
- Cancer-related Molecular Pathways
- Histone Deacetylase Inhibitors Research
- Ubiquitin and proteasome pathways
- Mitochondrial Function and Pathology
- Genomics and Chromatin Dynamics
- Pluripotent Stem Cells Research
- Cancer-related molecular mechanisms research
- Genetics and Neurodevelopmental Disorders
- CRISPR and Genetic Engineering
- Enzyme Structure and Function
- Kruppel-like factors research
- Microtubule and mitosis dynamics
- Circadian rhythm and melatonin
- Wnt/β-catenin signaling in development and cancer
- Bacterial Genetics and Biotechnology
- Carcinogens and Genotoxicity Assessment
- MicroRNA in disease regulation
- Cancer, Hypoxia, and Metabolism
- Bladder and Urothelial Cancer Treatments
- Sphingolipid Metabolism and Signaling
- Autophagy in Disease and Therapy
University of Nevada, Las Vegas
2013-2024
University of Science and Technology of China
2024
Qilu Hospital of Shandong University
2020-2024
Shanghai East Hospital
2023-2024
Peking University
2006-2023
Emory University
2012-2023
Qingdao University
2023
Affiliated Hospital of Qingdao University
2023
Shanghai Jiao Tong University
2023
University of Illinois Chicago
2023
To ensure survival in the face of genomic insult, cells have evolved complex mechanisms to respond DNA damage, termed damage checkpoint. The serine/threonine kinases ataxia telangiectasia-mutated (ATM) and ATM Rad3-related (ATR) activate checkpoint signaling by phosphorylating substrate proteins at SQ/TQ motifs. Although some ATM/ATR substrates (Chk1, p53) been identified, lack a more complete list limits current understanding pathways. Here, we use immunoaffinity phosphopeptide isolation...
Histone modification determines epigenetic patterns of gene expression with methylation histone H3 at lysine 4 (H3K4) often associated active promoters. LSD1/KDM1 is a demethylase that suppresses by converting dimethylated H3K4 to mono- and unmethylated H3K4. LSD1 essential for metazoan development, but its pathophysiologic functions in cancer remain mainly uncharacterized. In this study, we developed specific bioactive small inhibitors enhance derepress epigenetically suppressed genes vivo....
Gene amplification of Sox2 at 3q26.33 is a common event in squamous cell carcinomas (SCCs) the lung and esophagus, as well several other cancers. Here, we show that expression LSD1/KDM1 histone demethylase significantly elevated Sox2-expressing SCCs. LSD1-specific inhibitors selectively impair growth SCCs, but not Sox2-negative cells. associated with sensitivity to LSD1 inhibition lung, breast, ovarian, carcinoma Inactivation reduces expression, promotes G1 cell-cycle arrest, induces genes...
Alteration of the control DNA replication and mitosis is considered to be a major cause genome instability. To investigate mechanism that controls stability, we used RNA silencing-interference technique (RNAi) eliminate Drosophila geminin homologue from Schneider D2 (SD2) cells. Silencing by RNAi in SD2 cells leads cessation asynchronous overreplication genome, with containing single giant nuclei partial ploidy between 4N 8N content. The effect deficiency completely suppressed cosilencing...
Sirtuin 2 (SIRT2) is a sirtuin family deacetylase that directs acetylome signaling, protects genome integrity, and murine tumor suppressor. We show SIRT2 replication stress responses by regulating the activity of cyclin-dependent kinase 9 (CDK9), protein required for recovery from arrest. deficiency results in sensitivity, impairment arrest, spontaneous accumulation A to foci chromatin, G2/M checkpoint deficit. interacts with deacetylates CDK9 at lysine 48 response manner partially dependent...
The ataxia telangiectasia-mutated and Rad3-related (ATR) kinase checkpoint pathway maintains genome integrity; however, the role of sirtuin 2 (SIRT2) acetylome in regulating this is not clear. We found that deacetylation ATR-interacting protein (ATRIP), a regulatory partner ATR, by SIRT2 potentiates ATR checkpoint. interacts with deacetylates ATRIP at lysine 32 (K32) response to replication stress. K32 drives autophosphorylation signaling facilitates DNA fork progression recovery stalled...
Abstract Background Aging‐associated osteoporosis is frequently seen in the elderly clinic, but efficient managements are limited because of unclear nosogenesis. The current study aims to investigate role melatonin on senescent bone marrow stromal cells (BMSCs) and underlying regulating mechanism. Methods Melatonin levels were tested by ELISA. Gene expression profiles performed RNA‐sequencing, enrichment H3K36me2 gene promoters was analyzed Chromatin Immunoprecipitation Sequencing...
Abstract A dysregulated hypothalamic-pituitary-adrenal (HPA) axis has repeatedly been demonstrated to play a fundamental role in psychiatric disorders and suicide, yet the mechanisms underlying this dysregulation are not clear. Decreased expression of glucocorticoid receptor (GR) gene, which is also susceptible epigenetic modulation, strong indicator impaired HPA control. In context teenage suicide-completers, we have systematically analyzed 5’UTR GR gene determine levels all exon-1...
Coactivator-associated arginine methyltransferase 1 (CARM1) belongs to the protein family. CARM1 has been reported be associated with high grade tumors in breast cancer. It still remains unknown expression pattern of cancer and its relationships clinicopathological characteristics molecular subtypes.Two hundred forty-seven invasive cases were collected prepared for tissue array. There thirty-seven benign glandular epithelium adjacent among these cases. Molecular subtype investigated using...
LSD1 is essential for the maintenance of pluripotency embryonic stem (ES) or carcinoma/teratocarcinoma (EC) cells. We have previously developed novel inhibitors that selectively inhibit ES/EC However, critical targets remain unclear. Here, we found interacts with histone deacetylase 1 (HDAC1) to regulate proliferation cells through acetylation H4 at lysine 16 (H4K16), which show a substrate HDAC1. The demethylase and HDAC1 activities were both inactivated if one them in complex was...
Abstract The purpose of this study is to determine the methylation status Transforming growth factor-beta-inducible gene-h3 (TGFBI) and its correlation with paclitaxel chemoresistance in ovarian cancer. TGFBI was examined cancer control groups by methylation-specific PCR (MSP) bisulfite sequencing (BSP). expression cell viability were compared Quantitative Real-Time PCR, Western Blotting MTT assay before after demethylating agent 5-aza-2'-deoxycytidine (5-aza-dc) treatment 6 lines (SKOV3,...
The extremophilic bacterium Deinococcus radiodurans exhibits an extraordinary resistance to ionizing radiation. Previous studies established that a protein named PprI, which exists only in the Deinococcus-Thermus family, acts as general switch orchestrate expression of number DNA damage response (DDR) proteins involved cellular radio-resistance. Here we show regulatory mechanism PprI depends on its Mn(2+)-dependent protease activity toward DdrO, transcription factor suppresses DDR genes’...
Many non-histone proteins are lysine methylated and a novel function of this modification is to trigger the proteolysis proteins. Here, we report that 142 DNMT1, major DNA methyltransferase preserves epigenetic inheritance methylation patterns during replication, demethylated by LSD1. A methyl-binding protein, L3MBTL3, binds K142-methylated DNMT1 recruits CRL4DCAF5 ubiquitin ligase degrade DNMT1. Both LSD1 PHF20L1 act primarily in S phase prevent degradation L3MBTL3-CRL4DCAF5. Mouse...
Abstract Limited core transcription factors and transcriptional cofactors have been shown to govern embryonic stem cell (ESC) circuitry pluripotency, but the molecular interactions between remains ill defined. Here, we analyzed protein–protein Oct4, Sox2, Klf4, Myc (abbreviated as OSKM) a large panel of cofactors. The data reveal both specific common OSKM We found that among SET1/MLL family H3K4 methyltransferases, Set1a specifically interacts with Oct4 this interaction is independent Wdr5....
ABSTRACT Hyperhomocysteinemia (HHcy) promotes atherogenesis by modification of histone acetylation patterns and regulation miRNA expression while the underlying molecular mechanisms are not well known. In this study, we investigated effects homocysteine (Hcy) on deacetylase 1 (HDAC1) tested our hypothesis that Hcy‐induced atherosclerosis is mediated increased HDAC1 expression, which regulated miR‐34a. The H3 at lysine 9 (H3K9ac) decreased in aorta ApoE −/− mice fed with high methionine diet,...
The mammalian target-of-rapamycin (mTOR) signaling pathway serves as a major regulator of cell growth, size, and metabolism. In vivo, mTOR exists in two complexes, both which contain the catalytic subunit mTOR, invariable mLST8, complex specific Raptor or Rictor, forming either rapamycin-sensitive mTORC1 rapamycin-insensitive mTORC2, respectively. exact functions Rictor these complexes are still unclear. Here we demonstrate that mTORC1-mediated events require function 26S proteasome....
The interplay between the Yamanaka factors (OCT4, SOX2, KLF4 and c-MYC) transcriptional/epigenetic co-regulators in somatic cell reprogramming is incompletely understood. Here, we demonstrate that histone H3 lysine 27 trimethylation (H3K27me3) demethylase JMJD3 plays conflicting roles mouse reprogramming. On one side, induces pro-senescence factor Ink4a degrades pluripotency regulator PHF20 a factor-independent manner. other specifically recruited by to reduce H3K27me3 at both enhancers...
Metabolic reprogramming is considered important in the pathogenesis of occlusive vasculopathy observed pulmonary hypertension (PH). However, mechanisms that link reprogrammed metabolism to aberrant expression genes, which modulate functional phenotypes cells PH, remain enigmatic. Herein, we demonstrate that, mice, hypoxia-induced PH was prevented by glucose-6-phosphate dehydrogenase deficiency (G6PD