Abstract：
:Histone H3 lysine 79 (H3K79) methylation is enriched on actively transcribed genes, and its misregulation is a hallmark of leukemia. Methylation of H3K79, which resides on the structured disk face of the nucleosome, is mediated by the Dot1L methyltransferase. Dot1L activity is part of a trans-histone crosstalk pathway, requiring prior histone H2B ubiquitylation of lysine 120 (H2BK120ub) for optimal activity. However, the molecular details describing both how Dot1L binds to the nucleosome and why Dot1L is activated by H2BK120 ubiquitylation are unknown. Here, we present the cryoelectron microscopy (cryo-EM) structure of Dot1L bound to a nucleosome reconstituted with site-specifically ubiquitylated H2BK120. The structure reveals that Dot1L engages the nucleosome acidic patch using a variant arginine anchor and occupies a conformation poised for methylation. In this conformation, Dot1L and ubiquitin interact directly through complementary hydrophobic surfaces. This study establishes a path to better understand Dot1L function in normal and leukemia cells.
journal_name
Cell Repjournal_title
Cell reportsauthors
Anderson CJ,Baird MR,Hsu A,Barbour EH,Koyama Y,Borgnia MJ,McGinty RKdoi
10.1016/j.celrep.2019.01.058subject
Has Abstractpub_date
2019-02-12 00:00:00pages
1681-1690.e5issue
7issn
2211-1247pii
S2211-1247(19)30087-7journal_volume
26pub_type
杂志文章相关文献
Cell Reports文献大全abstract：:Alzheimer's disease (AD) is the most common form of dementia, impairing cognitive and motor functions. One of the pathological hallmarks of AD is neuronal loss, which is not reflected in mouse models of AD. Therefore, the role of neuronal death is still uncertain. Here, we used a Drosophila AD model expressing a secre...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2018.11.098
更新日期：2018-12-26 00:00:00
abstract：:Striatal medium-sized spiny neurons (MSNs), composed of striatonigral and striatopallidal neurons, are derived from the lateral ganglionic eminence (LGE). We find that the transcription factor Sp9 is expressed in LGE progenitors that generate nearly all striatal MSNs and that Sp9 expression is maintained in postmitoti...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2016.06.090
更新日期：2016-08-02 00:00:00
abstract：:Drosophila neuroblasts (NBs) have emerged as a model for stem cell biology that is ideal for genetic analysis but is limited by the lack of cell-type-specific gene expression data. Here, we describe a method for isolating large numbers of pure NBs and differentiating neurons that retain both cell-cycle and lineage cha...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2012.07.008
更新日期：2012-08-30 00:00:00
abstract：:Hypertrophic cardiomyopathy (HCM) is a heritable cardiovascular disorder that affects 1 in 500 people. A significant percentage of HCM is attributed to mutations in β-cardiac myosin, the motor protein that powers ventricular contraction. This study reports how two early-onset HCM mutations, D239N and H251N, affect the...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2016.11.040
更新日期：2016-12-13 00:00:00
abstract：:In fission yeast, the transcription factor Pap1 undergoes H2O2-dependent oxidation that promotes its nuclear accumulation and the activation of an antioxidant gene program. However, the mechanisms that regulate the sensitivity and selectivity of Pap1 activation by peroxides are not fully understood. Here, we demonstra...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2013.11.027
更新日期：2013-12-12 00:00:00
abstract：:Riboswitches are mRNA elements regulating gene expression in response to direct binding of a metabolite. While these RNAs are increasingly well understood with respect to interactions between receptor domains and their cognate effector molecules, little is known about the specific mechanistic relationship between meta...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2016.03.087
更新日期：2016-05-03 00:00:00
abstract：:The health of neurons is critically dependent on the relative signaling intensities of survival-promoting synaptic and death-inducing extrasynaptic NMDA receptors. Here, we show that BDNF is a regulator of this balance and promotes neuroprotection by reducing toxic NMDA receptor signaling. BDNF acts by initiating syna...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2015.07.038
更新日期：2015-08-25 00:00:00
abstract：:Parkinson's disease (PD) has been attributed to a combination of genetic and nongenetic factors. We studied a set of monozygotic twins harboring the heterozygous glucocerebrosidase mutation (GBA N370S) but clinically discordant for PD. We applied induced pluripotent stem cell (iPSC) technology for PD disease modeling ...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2014.10.023
更新日期：2014-11-20 00:00:00
abstract：:Oligodendrocyte progenitors (OPs) arise from distinct ventral and dorsal domains within the ventricular germinal zones of the embryonic CNS. The functional significance, if any, of these different populations is not known. Using dual-color reporter mice to distinguish ventrally and dorsally derived OPs, we show that, ...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2016.03.069
更新日期：2016-04-26 00:00:00
abstract：:Activation of postsynaptic metabotropic glutamate receptors (mGluRs) modulates neuronal excitability and synaptic plasticity, while deregulation of mGluR signaling has been implicated in neurodevelopmental disorders. Overstimulation of mGluRs is restricted by the rapid endocytosis of receptors after activation. Howeve...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2019.08.102
更新日期：2019-10-08 00:00:00
abstract：:In Drosophila larvae, the class IV dendritic arborization (da) neurons are polymodal nociceptors. Here, we show that ppk26 (CG8546) plays an important role in mechanical nociception in class IV da neurons. Our immunohistochemical and functional results demonstrate that ppk26 is specifically expressed in class IV da ne...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2014.10.020
更新日期：2014-11-20 00:00:00
abstract：:Alzheimer's disease (AD) is a neurodegenerative disease biochemically characterized by aberrant protein aggregation, including amyloid beta (Aβ) peptide accumulation. Protein aggregates in the cell are cleared by autophagy, a mechanism impaired in AD. To investigate the role of autophagy in Aβ pathology in vivo, we cr...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2013.08.042
更新日期：2013-10-17 00:00:00
abstract：:Most current tumor immunotherapy strategies leverage cytotoxic CD8+ T cells. Despite evidence for clinical potential of CD4+ tumor-infiltrating lymphocytes (TILs), their functional diversity limits our ability to harness their activity. Here, we use single-cell mRNA sequencing to analyze the response of tumor-specific...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2019.10.131
更新日期：2019-12-03 00:00:00
abstract：:Monkeys are an optimal model species for developing stem cell therapies. We previously reported generating chimeric cynomolgus monkey fetuses using dome-shaped embryonic stem cells (dESCs). However, conventional primed pluripotent stem cells (pPSCs) lack chimera competency. Here, by altering the media in which injecte...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2018.11.001
更新日期：2018-11-27 00:00:00
abstract：:Adipocytes deficient in fatty acid synthase (iAdFASNKO) emit signals that mimic cold exposure to enhance the appearance of thermogenic beige adipocytes in mouse inguinal white adipose tissues (iWATs). Both cold exposure and iAdFASNKO upregulate the sympathetic nerve fiber (SNF) modulator Neuregulin 4 (Nrg4), activate ...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2020.107998
更新日期：2020-08-04 00:00:00
abstract：:Hox genes are required for the development of the intestinal cecum, a major organ of plant-eating species. We have analyzed the transcriptional regulation of Hoxd genes in cecal buds and show that they are controlled by a series of enhancers located in a gene desert flanking the HoxD cluster. The start site of two opp...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2013.09.002
更新日期：2013-10-17 00:00:00
abstract：:Genetic differences between humans and in vivo model systems, including mice and nonhuman primates, make it difficult to predict the efficacy of immunoglobulin G (IgG) activity in humans and understand the molecular and cellular mechanisms underlying that activity. To bridge this gap, we established a small-animal mod...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2014.02.041
更新日期：2014-04-10 00:00:00
abstract：:APOBEC family cytidine deaminases have recently been implicated as powerful mutators of cancer genomes. How APOBECs, which are ssDNA-specific enzymes, gain access to chromosomal DNA is unclear. To ascertain the chromosomal ssDNA substrates of the APOBECs, we expressed APOBEC3A and APOBEC3B, the two most probable APOBE...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2016.01.021
更新日期：2016-02-16 00:00:00
abstract：:Self-reactive CD4 T cells are incompletely deleted during thymic development, and their peripheral seeding highlights the need for additional safeguards to avert autoimmunity. Here, we show an essential role for the coinhibitory molecule programmed death-1 (PD-1) in silencing the activation of high-affinity autoreacti...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2016.10.042
更新日期：2016-11-08 00:00:00
abstract：:The Hippo signaling pathway maintains organ size and tissue homeostasis via orchestration of cell proliferation and apoptosis. How this pathway triggers cell apoptosis remains largely unexplored. Here, we identify NR4A1 as a target of the Hippo pathway that mediates the pro-apoptotic and anti-tumor effects of the Hipp...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2020.108284
更新日期：2020-10-20 00:00:00
abstract：:In many organs, stem cell function depends on communication with their niche partners. Cranial sensory neurons develop in close proximity to blood vessels; however, whether vasculature is an integral component of their niches is yet unknown. Here, two separate roles for vasculature in cranial sensory neurogenesis in z...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2020.107903
更新日期：2020-07-14 00:00:00
abstract：:Innate immunity is central to the pathophysiology of neurodegenerative disorders, but it remains unclear why immunity is altered in the disease state and whether changes in immunity are a cause or a consequence of neuronal dysfunction. Here, we identify a molecular pathway that links innate immunity to age-dependent l...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2018.12.025
更新日期：2019-01-02 00:00:00
abstract：:Large-scale, cooperative rearrangements underlie the functions of RNA in RNA-protein machines and gene regulation. To understand how such rearrangements are orchestrated, we used high-throughput chemical footprinting to dissect a seemingly concerted rearrangement in P5abc RNA, a paradigm of RNA folding studies. With m...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2018.02.101
更新日期：2018-03-20 00:00:00
abstract：:α-Actinins, a family of critical cytoskeletal actin-binding proteins that usually exist as anti-parallel dimers, play crucial roles in organizing the framework of the cytoskeleton through crosslinking the actin filaments, as well as in focal adhesion maturation. However, the molecular mechanisms underlying its functio...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2017.11.040
更新日期：2017-12-05 00:00:00
abstract：:Katanin was the first microtubule (MT)-severing enzyme discovered, but how katanin executes MT severing remains poorly understood. Here, we report X-ray crystal structures of the apo and ATPγS-bound states of the catalytic AAA domain of human katanin p60 at 3.0 and 2.9 Å resolution, respectively. Comparison of the two...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2019.01.020
更新日期：2019-01-29 00:00:00
abstract：:X-linked inhibitor of apoptosis protein (XIAP) has been identified as a potent regulator of innate immune responses, and loss-of-function mutations in XIAP cause the development of the X-linked lymphoproliferative syndrome type 2 (XLP-2) in humans. Using gene-targeted mice, we show that loss of XIAP or deletion of its...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2014.05.008
更新日期：2014-06-26 00:00:00
abstract：:Fc receptor for IgM (FcμR)-deficient mice display dysregulated function of neutrophils, dendritic cells, and B cells. The relevance of FcμR to human T cells is still unknown. We show that FcμR is mostly stored inside the cell and that surface expression is tightly regulated. Decreased surface expression on T cells fro...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2019.02.024
更新日期：2019-03-05 00:00:00
abstract：:Palmitoylation is a reversible post-translational lipid modification that facilitates vesicular transport and subcellular localization of modified proteins. This process is catalyzed by ZDHHC enzymes that are implicated in several neurological and neurodevelopmental disorders. Loss-of-function mutations in ZDHHC9 have...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2019.10.065
更新日期：2019-11-19 00:00:00
abstract：:The small GTPase RhoA is involved in a variety of fundamental processes in normal tissue. Spatiotemporal control of RhoA is thought to govern mechanosensing, growth, and motility of cells, while its deregulation is associated with disease development. Here, we describe the generation of a RhoA-fluorescence resonance e...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2017.09.022
更新日期：2017-10-03 00:00:00
abstract：:Ependymomas exist within distinct genetic subgroups, but the molecular diversity within individual ependymomas is unknown. We perform multiplatform molecular profiling of 6 spatially distinct samples from an ependymoma with C11orf95-RELA fusion. DNA methylation and RNA sequencing distinguish clusters of samples accord...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2020.01.018
更新日期：2020-02-04 00:00:00
