Abstract:
:Long-lasting forms of synaptic plasticity such as synaptic scaling are critically dependent on transcription. Activity-dependent transcriptional dynamics in neurons, however, remain incompletely characterized because most previous efforts relied on measurement of steady-state mRNAs. Here, we use nascent RNA sequencing to profile transcriptional dynamics of primary neuron cultures undergoing network activity shifts. We find pervasive transcriptional changes, in which ∼45% of expressed genes respond to network activity shifts. We further link retinoic acid-induced 1 (RAI1), the Smith-Magenis syndrome gene, to the transcriptional program driven by reduced network activity. Remarkable agreement among nascent transcriptomes, dynamic chromatin occupancy of RAI1, and electrophysiological properties of Rai1-deficient neurons demonstrates the essential roles of RAI1 in suppressing synaptic upscaling in the naive network, while promoting upscaling triggered by activity silencing. These results highlight the utility of bona fide transcription profiling to discover mechanisms of activity-dependent chromatin remodeling that underlie normal and pathological synaptic plasticity.
journal_name
Cell Repjournal_title
Cell reportsauthors
Garay PM,Chen A,Tsukahara T,Rodríguez Díaz JC,Kohen R,Althaus JC,Wallner MA,Giger RJ,Jones KS,Sutton MA,Iwase Sdoi
10.1016/j.celrep.2020.108002subject
Has Abstractpub_date
2020-08-11 00:00:00pages
108002issue
6issn
2211-1247pii
S2211-1247(20)30987-6journal_volume
32pub_type
杂志文章相关文献
Cell Reports文献大全abstract::DNA methylation plays crucial roles in chromatin structure and gene expression. Aberrant DNA methylation patterns, including global hypomethylation and regional hypermethylation, are associated with cancer and implicated in oncogenic events. How DNA methylation is regulated in developmental and cellular processes and ...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2017.11.082
更新日期:2017-12-19 00:00:00
abstract::Blood flow regulation in pancreatic islets is critical for function but poorly understood. Here, we establish an in vivo imaging platform in a non-human primate where islets transplanted autologously into the anterior chamber of the eye are monitored non-invasively and longitudinally at single-cell resolution. Engraft...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2017.07.039
更新日期:2017-08-08 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::Early infantile epileptic encephalopathies (EOEE) are a debilitating spectrum of disorders associated with cognitive impairments. We present a clinical report of a KCNT2 mutation in an EOEE patient. The de novo heterozygous variant Phe240Leu SLICK was identified by exome sequencing and confirmed by Sanger sequencing. ...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2017.09.088
更新日期:2017-10-24 00:00:00
abstract::Endophilin-A, a well-characterized endocytic adaptor essential for synaptic vesicle recycling, has recently been linked to neurodegeneration. We report here that endophilin-A deficiency results in impaired movement, age-dependent ataxia, and neurodegeneration in mice. Transcriptional analysis of endophilin-A mutant mi...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2016.09.058
更新日期:2016-10-18 00:00:00
abstract::The Zika virus (ZIKV) poses a major public health emergency. To aid in the development of antivirals, we present two high-resolution crystal structures of the ZIKV NS5 methyltransferase: one bound to S-adenosylmethionine (SAM) and the other bound to SAM and 7-methyl guanosine diphosphate (7-MeGpp). We identify feature...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2016.08.091
更新日期:2016-09-20 00:00:00
abstract::Synapses are fundamental to the normal function of the nervous system. Glia play a pivotal role in regulating synaptic formation. However, how presynaptic neurons assemble synaptic structure in response to the glial signals remains largely unexplored. To address this question, we use cima-1 mutant C. elegans as an in ...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2020.01.102
更新日期:2020-02-25 00:00:00
abstract::Current treatment regimens for pancreatic ductal adenocarcinoma (PDAC) yield poor 5-year survival, emphasizing the critical need to identify druggable targets essential for PDAC maintenance. We developed an unbiased and in vivo target discovery approach to identify molecular vulnerabilities in low-passage and patient-...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2016.05.063
更新日期:2016-06-28 00:00:00
abstract::The epithelial-specific splicing regulators Esrp1 and Esrp2 are required for mammalian development, including establishment of epidermal barrier functions. However, the mechanisms by which Esrp ablation causes defects in epithelial barriers remain undefined. We determined that the ablation of Esrp1 and Esrp2 impairs e...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2018.10.097
更新日期:2018-11-27 00:00:00
abstract::The large number of mutations identified across all cancers represents an untapped reservoir of targets that can be useful for therapeutic targeting if highly selective, mutation-specific reagents are available. We report here our attempt to generate such reagents: monoclonal antibodies against the most common R175H, ...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2017.11.112
更新日期:2018-01-02 00:00:00
abstract::In vivo axon pathfinding mechanisms in the neuron-dense brain remain relatively poorly characterized. We study the Drosophila mushroom body (MB) axons, whose α and β branches connect to different brain areas. We show that the Ryk family WNT5 receptor, DRL (derailed), which is expressed in the dorsomedial lineages, bra...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2015.04.035
更新日期:2015-05-26 00:00:00
abstract::Isotope-based assessment of metabolic flux is achieved through a judicious balance of measurements and assumptions. Recent publications debate the validity of key assumptions used to model stable isotope labeling of liver metabolism in vivo. Here, we examine the controversy surrounding estimates of liver citric acid c...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2020.107986
更新日期:2020-08-04 00:00:00
abstract::People tend to fall asleep when gently rocked or vibrated. Experimental studies have shown that rocking promotes sleep in humans and mice. However, the mechanisms underlying the phenomenon are not well understood. A habituation model proposes that habituation, a form of non-associative learning, mediates sleep inducti...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2020.108462
更新日期:2020-12-01 00:00:00
abstract::Plant glutamate receptor homologs (GLRs) have long been proposed to function as ligand-gated Ca2+ channels, but no in planta evidence has been provided. Here, we present genetic evidence that Arabidopsis GLR3.1 and GLR3.5 form Ca2+ channels activated by L-methionine (L-Met) at physiological concentrations and regulate...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2016.11.015
更新日期:2016-12-06 00:00:00
abstract::The use of retinal organoids requires efficient differentiation from induced pluripotent stem cells (iPSCs). In this issue of Cell Reports, Wang et al. (2018) examine how the chromatin landscape after iPSC programming predicts their ability to differentiate into retinal tissue. ...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2018.02.078
更新日期:2018-03-06 00:00:00
abstract::The transcription factor NKX2-1 is best known for its role in the specification of subsets of cortical, striatal, and pallidal neurons. We demonstrate through genetic fate mapping and intersectional focal septal deletion that NKX2-1 is selectively required in the embryonic septal neuroepithelium for the development of...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2017.07.053
更新日期:2017-08-15 00:00:00
abstract::RNAi screens have implicated hundreds of host proteins as HIV-1 dependency factors (HDFs). While informative, these early studies overlap poorly due to false positives and false negatives. To ameliorate these issues, we combined information from the existing HDF screens together with new screens performed with multipl...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2014.09.031
更新日期:2014-10-23 00:00:00
abstract::Maintenance of skeletal muscle mass requires a dynamic balance between protein synthesis and tightly controlled protein degradation by the calpain, autophagy-lysosome, and ubiquitin-proteasome systems (proteostasis). Several sensing and gene-regulatory mechanisms act together to maintain this balance in response to ch...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2018.06.017
更新日期:2018-07-03 00:00:00
abstract::Health and survival in old age can be improved by changes in gene expression. RNA polymerase (Pol) I is the essential, conserved enzyme whose task is to generate the pre-ribosomal RNA (rRNA). We find that reducing the levels of Pol I activity is sufficient to extend lifespan in the fruit fly. This effect can be recapi...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2020.01.017
更新日期:2020-02-11 00:00:00
abstract::The Hedgehog (Hh) and Wnt/β-Catenin (Wnt) cascades are morphogen pathways whose pronounced influence on adult liver metabolism has been identified in recent years. How both pathways communicate and control liver metabolic functions are largely unknown. Detecting core components of Wnt and Hh signaling and mathematical...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2019.11.104
更新日期:2019-12-24 00:00:00
abstract::A central paradigm in the field of lymphocyte biology asserts that replicatively senescent memory T cells express the carbohydrate epitope CD57. These cells nonetheless accumulate with age and expand numerically in response to persistent antigenic stimulation. Here, we use in vivo deuterium labeling and ex vivo analys...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2020.108501
更新日期:2020-12-15 00:00:00
abstract::RIPK3 mediates cell death and regulates inflammatory responses. Although genetic studies have suggested that RIPK3-MLKL-mediated necroptosis leads to embryonic lethality in Fadd or Caspase-8-deficient mice, the exact mechanisms are not fully understood. Here, we generated Ripk3 mutant mice by altering the RIPK3 kinase...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2017.04.011
更新日期:2017-04-25 00:00:00
abstract::The kidney has a tremendous capacity to regenerate following injury, but factors that govern this response are still largely unknown. We isolated cells from mouse kidneys with high proliferative and multi-lineage differentiation capacity. These cells expressed a high level of Sox9. In regenerating kidneys, Sox9 expres...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2015.12.071
更新日期:2016-02-02 00:00:00
abstract::The guardian of the genome, p53, is often mutated in cancer and may contribute to therapeutic resistance. Given that p53 is intact and functional in normal tissues, we harnessed its potential to inhibit the growth of p53-deficient cancer cells. Specific activation of p53 in normal fibroblasts selectively induced apopt...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2013.12.020
更新日期:2014-01-30 00:00:00
abstract::The RNA binding proteins Rbfox1/2/3 regulate alternative splicing in the nervous system, and disruption of Rbfox1 has been implicated in autism. However, comprehensive identification of functional Rbfox targets has been challenging. Here, we perform HITS-CLIP for all three Rbfox family members in order to globally map...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2014.02.005
更新日期:2014-03-27 00:00:00
abstract::Common fragile sites (CFSs) are genomic regions that display gaps and breaks in human metaphase chromosomes under replication stress and are often deleted in cancer cells. We studied an ∼300-bp subregion (Flex1) of human CFS FRA16D in yeast and found that it recapitulates characteristics of CFS fragility in human cell...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2019.03.103
更新日期:2019-04-23 00:00:00
abstract::Evolutionary expansion of the human neocortex is partially attributed to a relative abundance of neural stem cells in the fetal brain called outer radial glia (oRG). oRG cells display a characteristic division mode, mitotic somal translocation (MST), in which the soma rapidly translocates toward the cortical plate imm...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2014.06.058
更新日期:2014-08-07 00:00:00
abstract::Chromatin regulation is driven by multicomponent protein complexes, which form functional modules. Deciphering the components of these modules and their interactions is central to understanding the molecular pathways these proteins are regulating, their functions, and their relation to both normal development and dise...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2014.05.050
更新日期:2014-07-10 00:00:00
abstract::Fibrillarin (FBL) is a dual-function nucleolar protein that catalyzes 2'-O methylation of pre-rRNA and methylation of histone H2A at glutamine 104 (H2AQ104me). The mechanisms that regulate FBL activity are unexplored. Here, we show that FBL is acetylated at several lysine residues by the acetyltransferase CBP and deac...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2018.11.051
更新日期:2018-12-11 00:00:00
abstract::A rare germline duplication upstream of the bone morphogenetic protein antagonist GREM1 causes a Mendelian-dominant predisposition to colorectal cancer (CRC). The underlying disease mechanism is strong, ectopic GREM1 overexpression in the intestinal epithelium. Here, we confirm that a common GREM1 polymorphism, rs1696...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2014.07.020
更新日期:2014-08-21 00:00:00