Abstract:
:Genome-wide profiling of histone modifications can provide systematic insight into the regulatory elements and programs engaged in a given cell type. However, conventional chromatin immunoprecipitation and sequencing (ChIP-seq) does not capture quantitative information on histone modification levels, requires large amounts of starting material, and involves tedious processing of each individual sample. Here, we address these limitations with a technology that leverages DNA barcoding to profile chromatin quantitatively and in multiplexed format. We concurrently map relative levels of multiple histone modifications across multiple samples, each comprising as few as a thousand cells. We demonstrate the technology by monitoring dynamic changes following inhibition of p300, EZH2, or KDM5, by linking altered epigenetic landscapes to chromatin regulator mutations, and by mapping active and repressive marks in purified human hematopoietic stem cells. Hence, this technology enables quantitative studies of chromatin state dynamics across rare cell types, genotypes, environmental conditions, and drug treatments.
journal_name
Mol Celljournal_title
Molecular cellauthors
van Galen P,Viny AD,Ram O,Ryan RJ,Cotton MJ,Donohue L,Sievers C,Drier Y,Liau BB,Gillespie SM,Carroll KM,Cross MB,Levine RL,Bernstein BEdoi
10.1016/j.molcel.2015.11.003subject
Has Abstractpub_date
2016-01-07 00:00:00pages
170-80issue
1eissn
1097-2765issn
1097-4164pii
S1097-2765(15)00863-1journal_volume
61pub_type
杂志文章相关文献
MOLECULAR CELL文献大全abstract::Aberrant folding and fibrillar aggregation by polyglutamine (polyQ) expansion proteins are associated with cytotoxicity in Huntington's disease and other neurodegenerative disorders. Hsp70 chaperones have an inhibitory effect on fibril formation and can alleviate polyQ cytotoxicity. Here we show that the cytosolic cha...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/j.molcel.2006.08.017
更新日期:2006-09-15 00:00:00
abstract::We show that the IRF-2 oncoprotein represses virus-induced IFN-beta gene transcription via a novel mechanism. Virus infection induces recruitment of IRF-2 to some of the endogenous IFN-beta enhancers as part of the enhanceosome. Enhanceosomes bearing IRF-2 cannot activate transcription, due to the presence of a domain...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/s1097-2765(05)00081-x
更新日期:2000-10-01 00:00:00
abstract::DNA replication is initiated by assembly of the kinase cell division cycle 7 (CDC7) with its regulatory activation subunit, activator of S-phase kinase (ASK), to activate DNA helicase. However, the mechanism underlying regulation of CDC7-ASK complex is unclear. Here, we show that ADP generated from CDC7-mediated MCM p...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/j.molcel.2018.09.007
更新日期:2018-11-15 00:00:00
abstract::Stress granules (SGs) are condensates of mRNPs that form in response to stress. SGs arise by multivalent protein-protein, protein-RNA, and RNA-RNA interactions. However, the role of RNA-RNA interactions in SG assembly remains understudied. Here, we describe a yeast SG reconstitution system that faithfully recapitulate...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/j.molcel.2020.07.017
更新日期:2020-09-17 00:00:00
abstract::BRCA1 functions at two distinct steps during homologous recombination (HR). Initially, it promotes DNA end resection, and subsequently it recruits the PALB2 and BRCA2 mediator complex, which stabilizes RAD51-DNA nucleoprotein filaments. Loss of 53BP1 rescues the HR defect in BRCA1-deficient cells by increasing resecti...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/j.molcel.2018.12.010
更新日期:2019-03-21 00:00:00
abstract::The ER-associated degradation (ERAD) pathway serves as an important cellular safeguard by directing incorrectly folded and unassembled proteins from the ER to the proteasome. Still, however, little is known about the components mediating ERAD of membrane proteins. Here we show that the evolutionary conserved rhomboid ...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/j.molcel.2012.06.008
更新日期:2012-08-24 00:00:00
abstract::The ability to measure human aging from molecular profiles has practical implications in many fields, including disease prevention and treatment, forensics, and extension of life. Although chronological age has been linked to changes in DNA methylation, the methylome has not yet been used to measure and compare human ...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/j.molcel.2012.10.016
更新日期:2013-01-24 00:00:00
abstract::The entry of human immunodeficiency virus (HIV-1) into cells is initiated by binding of the gp120 exterior envelope glycoprotein to the receptor, CD4. How does CD4 binding trigger conformational changes in gp120 that allow the gp41 transmembrane envelope glycoprotein to mediate viral-cell membrane fusion? The transiti...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/j.molcel.2010.02.012
更新日期:2010-03-12 00:00:00
abstract::In response to hyperosmotic environments, most eukaryotic cells activate a specialized mitogen-activated protein (MAP) kinase pathway. In S. cerevisiae, the key protein kinase, Hog1, coordinates the transcriptional induction of a variety of genes devoted to osmoadaptation and general stress protection. Depending on th...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/s1097-2765(01)00221-0
更新日期:2001-04-01 00:00:00
abstract::Mutations in Hnf-1alpha are the most common Mendelian cause of diabetes mellitus. To elucidate the molecular function of a mutational hotspot, we cocrystallized human HNF-1alpha 83-279 with a high-affinity promoter and solved the structure of the complex. Two identical protein molecules are bound to the promoter. Each...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/s1097-2765(02)00704-9
更新日期:2002-11-01 00:00:00
abstract::In this issue of Molecular Cell, Chen et al. (2014) provide evidence that FMRP represses translation by binding the ribosome, suggesting a novel form of translational control. ...
journal_title:Molecular cell
pub_type: 评论,杂志文章
doi:10.1016/j.molcel.2014.04.027
更新日期:2014-05-08 00:00:00
abstract::Posttranslational histone modifications participate in modulating the structure and function of chromatin. Promoters of transcribed genes are enriched with K4 trimethylation and hyperacetylation on the N-terminal tail of histone H3. Recently, PHD finger proteins, like Yng1 in the NuA3 HAT complex, were shown to intera...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/j.molcel.2006.10.026
更新日期:2006-12-08 00:00:00
abstract::Cellular stress results in profound changes in RNA and protein synthesis. How cells integrate this intrinsic, p53-centered program with extracellular signals is largely unknown. We demonstrate that TGF-β1 signaling interferes with the stress response through coordinate transcriptional and translational repression of p...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/j.molcel.2013.04.029
更新日期:2013-05-23 00:00:00
abstract::A variety of debilitating diseases including diabetes, Alzheimer's, Huntington's, Parkinson's, and prion-based diseases are linked to stress within the endoplasmic reticulum (ER). Using S. cerevisiae, we sought to determine the relationship between protein misfolding, ER stress, and cell death. In the absence of ERV29...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/j.molcel.2004.08.025
更新日期:2004-09-10 00:00:00
abstract::Target site choice is a complex and poorly understood aspect of DNA transposition despite its importance in rational transposon-mediated gene delivery. Though most transposons choose target sites essentially randomly or with some slight sequence or structural preferences, insertion sequence IS608 from Helicobacter pyl...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/j.molcel.2009.05.017
更新日期:2009-06-12 00:00:00
abstract::Oocyte quality control culls eggs with defects in meiosis. In mouse, oocyte death can be triggered by defects in chromosome synapsis and recombination, which involve repair of DNA double-strand breaks (DSBs) between homologous chromosomes. We show that RNF212, a SUMO ligase required for crossing over, also mediates oo...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/j.molcel.2018.08.031
更新日期:2018-10-18 00:00:00
abstract::In this issue of Molecular Cell, Lu et al. (2019) analyze the role of the length and sequence complexity of the RNA polymerase II unstructured C-terminal domain in animal viability, development, and the dynamics of RNA polymerase II in vivo. ...
journal_title:Molecular cell
pub_type: 评论,杂志文章
doi:10.1016/j.molcel.2019.03.004
更新日期:2019-03-21 00:00:00
abstract::Eukaryotic gene expression regulation involves thousands of distal regulatory elements. Understanding the quantitative contribution of individual enhancers to gene expression is critical for assessing the role of disease-associated genetic risk variants. Yet, we lack the ability to accurately link genes with their dis...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/j.molcel.2020.09.005
更新日期:2020-10-15 00:00:00
abstract::In bacterial and archaeal CRISPR immune pathways, DNA sequences from invading bacteriophage or plasmids are integrated into CRISPR loci within the host genome, conferring immunity against subsequent infections. The ribonucleoprotein complex Cascade utilizes RNAs generated from these loci to target complementary "nonse...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/j.molcel.2012.03.020
更新日期:2012-06-08 00:00:00
abstract::Spongiform encephalopathies are believed to be transmitted by a unique mechanism involving self-propagating conformational conversion of prion protein into a misfolded form. Here we demonstrate that fundamental aspects of mammalian prion propagation, including the species barrier and strain diversity, can be reproduce...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/s1097-2765(04)00155-8
更新日期:2004-04-09 00:00:00
abstract::Recent work from Kuehner and Brow (2008) and Thiebaut et al. (2008) in Molecular Cell and Jenks et al. (2008) in Molecular and Cellular Biology reveals that regulated expression of central nucleotide synthesis pathway components directs start site-dependent RNA polymerase II termination. ...
journal_title:Molecular cell
pub_type: 评论,杂志文章
doi:10.1016/j.molcel.2008.08.014
更新日期:2008-09-05 00:00:00
abstract::Mitochondrial diseases and aging are associated with defects in the oxidative phosphorylation machinery (OXPHOS), which are the only complexes composed of proteins encoded by separate genomes. To better understand genome coordination and OXPHOS recovery during mitochondrial dysfunction, we examined ATFS-1, a transcrip...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/j.molcel.2015.02.008
更新日期:2015-04-02 00:00:00
abstract::The interaction of transcription factors with target genes is highly dynamic. Whether the dynamic nature of these interactions is merely an intrinsic property of transcription factors or serves a regulatory role is unknown. Here we have used single-cell fluorescence imaging combined with computational modeling and chr...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/j.molcel.2008.04.021
更新日期:2008-05-23 00:00:00
abstract::In this issue, Takahara and Maeda (2012) discover that together, Pbp1 and sequestration of the TORC1 complex in cytoplasmic mRNP stress granules provides a negative regulatory mechanism for TORC1 signaling during stress. ...
journal_title:Molecular cell
pub_type: 评论,杂志文章
doi:10.1016/j.molcel.2012.07.005
更新日期:2012-07-27 00:00:00
abstract::In a recent issue of Molecular Cell, Jia et al. (2008) demonstrate that time-controlled repression of interferon-induced transcripts depends upon the interaction between an RNA structure in these transcripts and protein domains harbored by a mammalian aminoacyl-tRNA synthetase. ...
journal_title:Molecular cell
pub_type: 评论,杂志文章
doi:10.1016/j.molcel.2008.03.006
更新日期:2008-04-11 00:00:00
abstract::Curli are extracellular functional amyloids that are assembled by enteric bacteria during biofilm formation and host colonization. An efficient secretion system and chaperone network ensures that the major curli fiber subunit, CsgA, does not form intracellular amyloid aggregates. We discovered that the periplasmic pro...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/j.molcel.2014.12.025
更新日期:2015-02-05 00:00:00
abstract::The CRISPR-associated protein Cas12a (Cpf1), which has been repurposed for genome editing, possesses two distinct nuclease activities: endoribonuclease activity for processing its own guide RNAs and RNA-guided DNase activity for target DNA cleavage. To elucidate the molecular basis of both activities, we determined cr...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/j.molcel.2017.03.016
更新日期:2017-04-20 00:00:00
abstract::Signals transmitted by ERK MAP kinases regulate the functions of multiple substrates present in the nucleus and in the cytoplasm. ERK signals are optimized by scaffold proteins that modulate their intensity and spatial fidelity. Once phosphorylated, ERKs dimerize, but how dimerization impacts on the activation of the ...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/j.molcel.2008.07.024
更新日期:2008-09-05 00:00:00
abstract::Multi-subunit SMC ATPases control chromosome superstructure and DNA topology, presumably by DNA translocation and loop extrusion. Chromosomal DNA is entrapped within the tripartite SMCkleisin ring. Juxtaposed SMC heads ("J heads") or engaged SMC heads ("E heads") split the SMCkleisin ring into "S" and "K" sub-compartm...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/j.molcel.2019.05.001
更新日期:2019-07-25 00:00:00
abstract::Prenylated Rab proteins exist in the cytosol as soluble, high-affinity complexes with GDI that need to be disrupted for membrane attachment and targeting of Rab proteins. The Legionella pneumophila protein DrrA displaces GDI from Rab1:GDI complexes, incorporating Rab1 into Legionella-containing vacuoles and activating...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/j.molcel.2009.11.014
更新日期:2009-12-25 00:00:00