A5101552257- Epigenetics and DNA Methylation
- Genomics and Chromatin Dynamics
- Cancer-related gene regulation
- Photochromic and Fluorescence Chemistry
- Protein Degradation and Inhibitors
- Ubiquitin and proteasome pathways
- Click Chemistry and Applications
- RNA Research and Splicing
- Acute Myeloid Leukemia Research
- Pluripotent Stem Cells Research
- DNA Repair Mechanisms
- Photoreceptor and optogenetics research
- RNA modifications and cancer
- Chromosomal and Genetic Variations
- Chemical Synthesis and Analysis
- Biochemical and Molecular Research
- Hematopoietic Stem Cell Transplantation
- Insect Resistance and Genetics
- Circular RNAs in diseases
- Multiple Myeloma Research and Treatments
- Gold and Silver Nanoparticles Synthesis and Applications
- Nanoparticles: synthesis and applications
- Genetics and Neurodevelopmental Disorders
- Cytomegalovirus and herpesvirus research
- Nanocluster Synthesis and Applications
University of Michigan–Ann Arbor
2014-2023
South China Agricultural University
2020
Howard Hughes Medical Institute
2017
Ann Arbor Center for Independent Living
2017
Chinese Academy of Sciences
2011
Institute of Intelligent Machines
2011
University of Science and Technology of China
2011
Institute of Plasma Physics
2011
Triple-negative breast cancers (TNBC) remain clinically challenging with a lack of options for targeted therapy. In this study, we report the development second-generation BET protein degrader, BETd-246, which exhibits superior selectivity, potency, and antitumor activity. human TNBC cells, BETd-246 induced degradation proteins at low nanomolar concentrations within 1 hour exposure, resulting in robust growth inhibition apoptosis. was more potent effective cells than its parental inhibitor...
We report herein the design, synthesis, and evaluation of macrocyclic peptidomimetics that bind to WD repeat domain 5 (WDR5) block WDR5-mixed lineage leukemia (MLL) protein-protein interaction. Compound 18 (MM-589) binds WDR5 with an IC50 value 0.90 nM (Ki <1 nM) inhibits MLL H3K4 methyltransferase (HMT) activity 12.7 nM. potently selectively cell growth in human lines harboring translocations is >40 times better than previously reported compound MM-401. Cocrystal structures 16 complexed...
Mixed lineage leukemia (MLL) family histone methyltransferases are enzymes that deposit H3 Lys4 (K4) mono-/di-/tri-methylation and regulate gene expression in mammals. Despite extensive structural biochemical studies, the molecular mechanisms whereby MLL complexes recognize H3K4 within nucleosome core particles (NCPs) remain unclear. Here we report single-particle cryo-electron microscopy (cryo-EM) structure of NCP-bound human MLL1 complex. We show complex anchors to NCP via conserved RbBP5...
Abstract Triangular gold nanoprisms with high yield percentage were synthesized via the seed‐mediated approach and functionalized by mono‐6‐thio‐β‐cyclodextrin without alkyl chain. The undecorated decorated triangular characterized analyzed. Moreover, novel used as surface‐enhanced Raman spectroscopy (SERS) substrates for chemical sensing of explosive agent 2,4‐dinitrotoluene (DNT). vibrational bands in experimental SERS spectrum assigned aid density functional theoretical simulation....
Rapidly cycling fetal and neonatal hematopoietic stem cells (HSCs) generate a pool of quiescent adult HSCs after establishing hematopoiesis in the bone marrow. We report an essential role for trithorax group gene absent, small, or homeotic 1-like (Ash1l) at this developmental transition. Emergence expansion Ash1l-deficient fetal/neonatal were preserved; however, young animals, profoundly depleted. had markedly decreased quiescence reduced cyclin-dependent kinase inhibitor 1b/c (Cdkn1b/1c)...
Abstract Recent cryo-EM structures show the highly dynamic nature of MLL1-NCP (nucleosome core particle) interaction. Functional implication and regulation such dynamics remain unclear. Here we that DPY30 intrinsically disordered regions (IDRs) ASH2L work together in restricting rotational MLL1 complex on NCP. We binding to leads stabilization integration IDRs into establishes new ASH2L-NCP contacts. The significance ASH2L-DPY30 interactions is demonstrated by requirement both for dramatic...
Shine light on epigenetics: we describe how photoswitchable peptidomimetics modulate the activity of MLLl enzyme affecting epigenetic states.
Abstract Mixed lineage leukemia protein-1 (MLL1) has a critical role in human MLL1 rearranged ( MLLr ) and is validated therapeutic target. However, its regulating global gene expression cells, as well interplay with fusion proteins remains unclear. Here we show that despite shared DNA-binding cofactor interacting domains at the N terminus, MLL-AF9 are recruited to distinct chromatin regions have divergent functions leukemic transcription program. We demonstrate MLL1, probably through...
Abstract Life relies on a myriad of carefully orchestrated processes, in which proteins and their direct interplay ultimately determine cellular function disease. Modulation this complex crosstalk has recently attracted attention, even as novel therapeutic strategy. Herein, we describe the synthesis characterization two visible‐light‐responsive peptide backbone photoswitches based azobenzene derivatives, to exert optical control over protein–protein interactions (PPI). The peptidomimetics...
How ubiquitous transcription factors (TFs) coordinate temporal inputs from broadly expressed epigenetic to control cell fate remains poorly understood. Here, we uncover a molecular relationship between p53, an abundant embryonic TF, and WDR5, essential member of the MLL chromatin modifying complex, that regulates mouse stem fate. Wild-type Wdr5 or transient knockout promotes distinct pattern global accessibility spurs neuroectodermal differentiation through RbBP5-dependent process in which...
Optical control has enabled functional modulation in cell culture with unparalleled spatiotemporal resolution. However, current tools for vivo manipulation are scarce. Here, we design and implement a genuine on-off optochemical probe capable of achieving hematopoietic zebrafish. Our photopharmacological approach first developed conformationally strained visible light photoswitches (CS-VIPs) as inhibitors the histone methyltransferase MLL1 (KMT2A). In blood homeostasis plays crucial yet...
Nanotechnology has clear potential in the development of innovative insecticidal products for biorational management major insect pests. Metal-based nanoparticles different microbial pest control agents have been effective against several Synthesis Beauveria brongniartii based Fe0 (Fe0NPs) and their bio-efficacy Spodoptera litura was observed during this study. conidia were coated with Fe0NPs characterized by applying a selection analytical techniques. Ultraviolet (UV) spectroscopy showed...
SUMMARY Mixed Lineage Leukemia (MLL) family histone methyltransferases are the key enzymes that deposit H3 Lys4 (K4) mono-/di-/tri-methylation and regulate gene expression in mammals. Despite extensive structural biochemical studies, molecular mechanism by which MLL complexes recognize H3K4 within nucleosome core particle (NCP) remains unclear. Here, we report single-particle cryo-electron microscopy (cryo-EM) structure of human MLL1 complex bound to NCP. The anchors on NCP through RbBP5...
Cell-type specific transcription factors cooperate with chromatin-modifying proteins to orchestrate proper differentiation, but little is known how ubiquitous embryonic coordinate inputs from broadly expressed epigenetic control cell fate. Here, we uncover a previously unappreciated molecular relationship between p53, an abundant protein, and Wdr5, essential member of the COMPASS chromatin modifying complex, that regulates mouse stem (ESC) Intact, or brief disruption of, Wdr5 activity...