A5078988723- Genomics and Chromatin Dynamics
- Epigenetics and DNA Methylation
- DNA Repair Mechanisms
- RNA modifications and cancer
- Cancer-related gene regulation
- CRISPR and Genetic Engineering
- Glioma Diagnosis and Treatment
- Ubiquitin and proteasome pathways
- RNA Research and Splicing
- Protein Degradation and Inhibitors
- Immune cells in cancer
- Pluripotent Stem Cells Research
- Histone Deacetylase Inhibitors Research
- Cancer-related Molecular Pathways
- Sperm and Testicular Function
- Reproductive Biology and Fertility
- Microtubule and mitosis dynamics
- Mitochondrial Function and Pathology
- Cancer-related molecular mechanisms research
- Chromosomal and Genetic Variations
- melanin and skin pigmentation
- Renal and related cancers
- RNA and protein synthesis mechanisms
- Autophagy in Disease and Therapy
- Bacterial Genetics and Biotechnology
State Key Laboratory of Synthetic Chemistry
2024-2025
Chinese Academy of Sciences
2011-2024
Shenzhen Institutes of Advanced Technology
2021-2024
Mayo Clinic in Arizona
2024
University of Minnesota
2024
City University of Hong Kong
2024
South China Agricultural University
2024
University of Macau
2024
University of Minnesota System
2024
St. Jude Children's Research Hospital
2020-2021
Recent studies have identified a Lys 27-to-methionine (K27M) mutation at one allele of H3F3A , the two genes encoding histone H3 variant H3.3, in 60% high-grade pediatric glioma cases. The median survival this group patients after diagnosis is ∼1 yr. Here we show that levels H3K27 di- and trimethylation (H3K27me2 H3K27me3) are reduced globally H3.3K27M patient samples due to expression mutant allele. Remarkably, also observed H3K27me3 Ezh2 (the catalytic subunit methyltransferase) chromatin...
A cancer-promoting histone protein Mutations in the chromatin H3 are found a number of pediatric cancers. The lysine-36–to–methionine (K36M) “oncohistone” mutation is seen almost all chondroblastomas. Fang et al. show that K36M mutant histones inhibit normal methylation this same residue wild-type histones. They do so by interfering with enzymes normally methylate residue. altered patterns alter expression known cancer-related genes and impart characteristics to chondrocyte cells. Science ,...
How parental histone (H3-H4)2 tetramers, the primary carriers of epigenetic modifications, are transferred onto leading and lagging strands DNA replication forks for inheritance remains elusive. Here we show that tetramers assembled into nucleosomes both strands, with a slight preference strands. The lagging-strand increases markedly in budding yeast cells lacking Dpb3 Dpb4, two subunits strand polymerase, Pol ε, owing to impairment transfer Dpb3-Dpb4 binds H3-H4 vitro participates...
Temozolomide (TMZ) was used for the treatment of glioblastoma (GBM) over a decade, but its benefits are limited by acquired resistance, process that remains incompletely understood. Here we report an enhancer, located between promoters marker proliferation Ki67 (MKI67) and O6-methylguanine-DNA-methyltransferase (MGMT) genes, is activated in TMZ-resistant patient-derived xenograft (PDX) lines recurrent tumor samples. Activation enhancer correlates with increased MGMT expression, major known...
miRNAs play important roles during mammalian spermatogenesis. However, the function of most in spermatogenesis and underlying mechanisms remain unknown. Here, we report that miR-202 is highly expressed mouse spermatogonial stem cells (SSCs), oppositely regulated by Glial cell-Derived Neurotrophic Factor (GDNF) retinoic acid (RA), two key factors for SSC self-renewal differentiation. We used inducible CRISPR-Cas9 to knockout cultured SSCs, found SSCs initiated premature differentiation...
Expression of histone H3.3K27M mutant proteins in human diffuse intrinsic pontine glioma (DIPG) results a global reduction tri-methylation H3K27 (H3K27me3), and paradoxically, H3K27me3 peaks remain at hundreds genomic loci, dichotomous change that lacks mechanistic insights. Here, we show the PRC2 complex is sequestered poised enhancers, but not active promoters with high levels proteins, thereby contributing to H3K27me3. Moreover, are low retained consequently having minimal effects on...
Faithful inheritance of parental histones is essential to maintain epigenetic information and cellular identity during cell division. Parental are evenly deposited onto the replicating DNA sister chromatids in a process dependent on MCM2 subunit helicase. However, impact aberrant histone partition human disease such as cancer largely unknown. In this study, we construct model impaired by introducing MCM2-2A mutation (defective binding) MCF-7 breast cells. The resulting reprograms...
PIWI-interacting RNAs (piRNAs) are a class of small abundantly expressed in animal gonads. piRNAs that map to retrotransposons generated by “ping-pong” amplification loop suppress the activity retrotransposons. However, biogenesis and function other categories have yet be investigated. In this study, we first profiled expression type A spermatogonia, pachytene spermatocytes, round spermatids deep sequencing. We then focused on computational analysis potential present study as well published...
Mammalian spermatogenesis consists of many cell types and biological processes serves as an excellent model for studying gene regulation at transcriptional post-transcriptional levels. Many key proteins, miRNAs, perhaps piRNAs have been shown to be involved in spermatogenesis. However, a systematic method assessing the relationship between protein mRNA expression has not available mechanisms regulation. In present study, we used iTRAQ-based quantitative proteomic approach identify 2008...
Chromatin replication is intricately intertwined with the recycling of parental histones to newly duplicated DNA strands for faithful genetic and epigenetic inheritance. The transfer occurs through two distinct pathways: leading strand deposition, mediated by polymerase ε subunits Dpb3/Dpb4, lagging facilitated MCM helicase subunit Mcm2. However, mechanism facilitation Mcm2 transferring while moving along remains unclear. Here, we show that deletion Pol32, a nonessential major lagging-strand...
Abstract Recycling of parental histones is an important step in epigenetic inheritance. During DNA replication, polymerase epsilon subunit DPB3/DPB4 and replication helicase MCM2 are involved the transfer to leading lagging strands, respectively. Single Dpb3 deletion (dpb3Δ) or Mcm2 mutation (mcm2-3A), which each disrupts one histone pathway, leads other's predominance. However, biological impact two pathways on chromatin structure repair remains elusive. In this study, we used budding yeast...
DNA replication is tightly regulated to occur once and only per cell cycle. How chromatin, the physiological substrate of machinery, regulates remains largely unknown. Here we show that histone H3 lysine 9 demethylase Kdm4d in eukaryotic cells. Depletion results defects replication, which can be rescued by expression H3K9M, a mutant transgene reverses effect on H3K9 methylation. interacts with proteins, its recruitment origins depends two pre-replicative complex components (origin...
DNA replication is a crucial biological process that ensures the accurate transmission of genetic information, underpinning growth, development, and reproduction organisms. Abnormalities in are primary source genomic instability tumorigenesis. During replication, assembly pre-RC at G1-G1/S transition licensing step successful initiation replication. Although many pre-replication complex (pre-RC) proteins have been identified, technical limitations hinder detection transiently interacting...
Glioblastoma (GBM) is the most aggressive primary brain tumor in human. Recent studies on high-grade pediatric GBM have identified two recurrent mutations (K27M and G34R/V) genes encoding histone H3 (H3F3A for H3.3 HIST1H3B H3.1).Citation1,Citation2 The are mutually exclusive give rise to tumors different compartments.Citation3 Recently, we4 others5 shown that K27M mutation specifically altered di- tri-methylation of endogenous at Lys27. Genome-wide using ChIP-seq H3.3K27M patient samples...
Spermatogenesis is sustained by the proliferation and differentiation of spermatogonial stem cells (SSCs). However, molecules controlling these processes remain largely unknown. Here, we developed a simplified high concentration serum‐containing system for culture mouse SSCs. Analysis SSCs markers transplantation results revealed that cultured spermatogonia retained cell characteristics after long‐term in vitro propagation. Using this system, expression function bone morphogenetic protein 4...