Publications by authors named "Samuel C Robson"

15 Publications

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The skin microbiome of Xenopus laevis and the effects of husbandry conditions.

Anim Microbiome 2021 Feb 5;3(1):17. Epub 2021 Feb 5.

Centre for Enzyme Innovation, University of Portsmouth, Portsmouth, UK.

Background: Historically the main source of laboratory Xenopus laevis was the environment. The increase in genetically altered animals and evolving governmental constraints around using wild-caught animals for research has led to the establishment of resource centres that supply animals and reagents worldwide, such as the European Xenopus Resource Centre. In the last decade, centres were encouraged to keep animals in a "low microbial load" or "clean" state, where embryos are surface sterilized before entering the housing system; instead of the conventional, "standard" conditions where frogs and embryos are kept without prior surface treatment. Despite Xenopus laevis having been kept in captivity for almost a century, surprisingly little is known about the frogs as a holobiont and how changing the microbiome may affect resistance to disease. This study examines how the different treatment conditions, "clean" and "standard" husbandry in recirculating housing, affects the skin microbiome of tadpoles and female adults. This is particularly important when considering the potential for poor welfare caused by a change in husbandry method as animals move from resource centres to smaller research colonies.

Results: We found strong evidence for developmental control of the surface microbiome on Xenopus laevis; adults had extremely similar microbial communities independent of their housing, while both tadpole and environmental microbiome communities were less resilient and showed greater diversity.

Conclusions: Our findings suggest that the adult Xenopus laevis microbiome is controlled and selected by the host. This indicates that the surface microbiome of adult Xenopus laevis is stable and defined independently of the environment in which it is housed, suggesting that the use of clean husbandry conditions poses little risk to the skin microbiome when transferring adult frogs to research laboratories. This will have important implications for frog health applicable to Xenopus laevis research centres throughout the world.
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http://dx.doi.org/10.1186/s42523-021-00080-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7866774PMC
February 2021

Complete transcriptome assembly and annotation of a critically important amphipod species in freshwater ecotoxicological risk assessment: Gammarus fossarum.

Environ Int 2020 04 3;137:105319. Epub 2020 Feb 3.

Institute of Marine Sciences, School of Biological Sciences, University of Portsmouth, Ferry Road, Portsmouth PO4 9LY, UK. Electronic address:

Because of their crucial role in ecotoxicological risk assessment, amphipods (Crustacea) are commonly employed as model species in a wide range of studies. However, despite their ecological importance, their genome has not yet been completely annotated and molecular mechanisms underlying key pathways, such as the serotonin pathway, in development of ecotoxicological biomarkers of exposure to neuroactive pharmaceuticals are still poorly understood. Furthermore, genetic similarities and discrepancies with other model arthropods (e.g., Drosophila melanogaster) have not been completely clarified. In this report, we present a new transcriptome assembly of Gammarus fossarum, an important amphipod species, widespread in Central Europe. RNA-Seq with Illumina HiSeq technology was used to analyse samples extracted from total internal tissues. We used the Trinity and Trinotate software suites for transcriptome assembly and annotation, respectively. The quality of this assembly and the affiliated targeted homology searches greatly enrich the molecular knowledge on this species. Because of the lack of publicly available molecular information on the serotonin pathway, we also highlighted sequence homologies and divergences of the genes encoding the serotonin pathway components of the well-annotated arthropod D. melanogaster, and Crustacea with the corresponding genes of our assembly. An inferior number of hits was found when running a BLAST analysis of both D. melanogaster and Crustacea mRNA sequences encoding serotonin receptors available in GenBank against the total assembly, compared to other serotonin pathway components. A lack of information on important components for serotonin biosynthesis and vesicle endocytosis (i.e., tryptophan hydroxylase and vesicular monoamine transporter) in Crustacea was also brought to light. Our results will provide an extensive transcriptional resource for this important species in ecotoxicological risk assessment and highlight the need for a more detailed categorization of neuronal pathways components in invertebrates.
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http://dx.doi.org/10.1016/j.envint.2019.105319DOI Listing
April 2020

Total Absence of Dystrophin Expression Exacerbates Ectopic Myofiber Calcification and Fibrosis and Alters Macrophage Infiltration Patterns.

Am J Pathol 2020 01 11;190(1):190-205. Epub 2019 Nov 11.

Laboratory of Molecular Medicine, School of Pharmacy and Biomedical Sciences, University of Portsmouth, Portsmouth, United Kingdom; Military Institute of Hygiene and Epidemiology, Warsaw, Poland. Electronic address:

Duchenne muscular dystrophy (DMD) causes severe disability and death of young men because of progressive muscle degeneration aggravated by sterile inflammation. DMD is also associated with cognitive and bone-function impairments. This complex phenotype results from the cumulative loss of a spectrum of dystrophin isoforms expressed from the largest human gene. Although there is evidence for the loss of shorter isoforms having impact in the central nervous system, their role in muscle is unclear. We found that at 8 weeks, the active phase of pathology in dystrophic mice, dystrophin-null mice (mdx) presented with a mildly exacerbated phenotype but without an earlier onset, increased serum creatine kinase levels, or decreased muscle strength. However, at 12 months, mdx diaphragm strength was lower, whereas fibrosis increased, compared with mdx. The most striking features of the dystrophin-null phenotype were increased ectopic myofiber calcification and altered macrophage infiltration patterns, particularly the close association of macrophages with calcified fibers. Ectopic calcification had the same temporal pattern of presentation and resolution in mdx and mdx muscles, despite significant intensity differences across muscle groups. Comparison of the rare dystrophin-null patients against those with mutations affecting full-length dystrophins may provide mechanistic insights for developing more effective treatments for DMD.
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http://dx.doi.org/10.1016/j.ajpath.2019.09.021DOI Listing
January 2020

Interaction of Sox2 with RNA binding proteins in mouse embryonic stem cells.

Exp Cell Res 2019 08 9;381(1):129-138. Epub 2019 May 9.

Laboratory of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden; Ming Wai Lau Centre for Reparative Medicine, Stockholm Node, Karolinska Institutet, Stockholm, Sweden. Electronic address:

Sox2 is a master transcriptional regulator of embryonic development. In this study, we determined the protein interactome of Sox2 in the chromatin and nucleoplasm of mouse embryonic stem (mES) cells. Apart from canonical interactions with pluripotency-regulating transcription factors, we identified interactions with several chromatin modulators, including members of the heterochromatin protein 1 (HP1) family, suggesting a role for Sox2 in chromatin-mediated transcriptional repression. Sox2 was also found to interact with RNA binding proteins (RBPs), including proteins involved in RNA processing. RNA immunoprecipitation followed by sequencing revealed that Sox2 associates with different messenger RNAs, as well as small nucleolar RNA Snord34 and the non-coding RNA 7SK. 7SK has been shown to regulate transcription at gene regulatory regions, which could suggest a functional interaction with Sox2 for chromatin recruitment. Nevertheless, we found no evidence of Sox2 modulating recruitment of 7SK to chromatin when examining 7SK chromatin occupancy by Chromatin Isolation by RNA Purification (ChIRP) in Sox2 depleted mES cells. In addition, knockdown of 7SK in mES cells did not lead to any change in Sox2 occupancy at 7SK-regulated genes. Thus, our results show that Sox2 extensively interacts with RBPs, and suggest that Sox2 and 7SK co-exist in a ribonucleoprotein complex whose function is not to regulate chromatin recruitment, but could rather regulate other processes in the nucleoplasm.
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http://dx.doi.org/10.1016/j.yexcr.2019.05.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6994247PMC
August 2019

METTL1 Promotes let-7 MicroRNA Processing via m7G Methylation.

Mol Cell 2019 06 25;74(6):1278-1290.e9. Epub 2019 Apr 25.

The Gurdon Institute and Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK. Electronic address:

7-methylguanosine (m7G) is present at mRNA caps and at defined internal positions within tRNAs and rRNAs. However, its detection within low-abundance mRNAs and microRNAs (miRNAs) has been hampered by a lack of sensitive detection strategies. Here, we adapt a chemical reactivity assay to detect internal m7G in miRNAs. Using this technique (Borohydride Reduction sequencing [BoRed-seq]) alongside RNA immunoprecipitation, we identify m7G within a subset of miRNAs that inhibit cell migration. We show that the METTL1 methyltransferase mediates m7G methylation within miRNAs and that this enzyme regulates cell migration via its catalytic activity. Using refined mass spectrometry methods, we map m7G to a single guanosine within the let-7e-5p miRNA. We show that METTL1-mediated methylation augments let-7 miRNA processing by disrupting an inhibitory secondary structure within the primary miRNA transcript (pri-miRNA). These results identify METTL1-dependent N7-methylation of guanosine as a new RNA modification pathway that regulates miRNA structure, biogenesis, and cell migration.
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http://dx.doi.org/10.1016/j.molcel.2019.03.040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6591002PMC
June 2019

SRPK1 maintains acute myeloid leukemia through effects on isoform usage of epigenetic regulators including BRD4.

Nat Commun 2018 12 19;9(1):5378. Epub 2018 Dec 19.

Haematological Cancer Genetics, Wellcome Trust Sanger Institute, Hinxton, Cambridge, CB10 1SA, UK.

We recently identified the splicing kinase gene SRPK1 as a genetic vulnerability of acute myeloid leukemia (AML). Here, we show that genetic or pharmacological inhibition of SRPK1 leads to cell cycle arrest, leukemic cell differentiation and prolonged survival of mice transplanted with MLL-rearranged AML. RNA-seq analysis demonstrates that SRPK1 inhibition leads to altered isoform levels of many genes including several with established roles in leukemogenesis such as MYB, BRD4 and MED24. We focus on BRD4 as its main isoforms have distinct molecular properties and find that SRPK1 inhibition produces a significant switch from the short to the long isoform at the mRNA and protein levels. This was associated with BRD4 eviction from genomic loci involved in leukemogenesis including BCL2 and MYC. We go on to show that this switch mediates at least part of the anti-leukemic effects of SRPK1 inhibition. Our findings reveal that SRPK1 represents a plausible new therapeutic target against AML.
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http://dx.doi.org/10.1038/s41467-018-07620-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6300607PMC
December 2018

Phosphorylation of Histone H4T80 Triggers DNA Damage Checkpoint Recovery.

Mol Cell 2018 11 25;72(4):625-635.e4. Epub 2018 Oct 25.

The Wellcome Trust/Cancer Research UK Gurdon Institute and Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK. Electronic address:

In response to genotoxic stress, cells activate a signaling cascade known as the DNA damage checkpoint (DDC) that leads to a temporary cell cycle arrest and activation of DNA repair mechanisms. Because persistent DDC activation compromises cell viability, this process must be tightly regulated. However, despite its importance, the mechanisms regulating DDC recovery are not completely understood. Here, we identify a DNA-damage-regulated histone modification in Saccharomyces cerevisiae, phosphorylation of H4 threonine 80 (H4T80ph), and show that it triggers checkpoint inactivation. H4T80ph is critical for cell survival to DNA damage, and its absence causes impaired DDC recovery and persistent cell cycle arrest. We show that, in response to genotoxic stress, p21-activated kinase Cla4 phosphorylates H4T80 to recruit Rtt107 to sites of DNA damage. Rtt107 displaces the checkpoint adaptor Rad9, thereby interrupting the checkpoint-signaling cascade. Collectively, our results indicate that H4T80ph regulates DDC recovery.
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http://dx.doi.org/10.1016/j.molcel.2018.09.023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6242705PMC
November 2018

Promoter-bound METTL3 maintains myeloid leukaemia by mA-dependent translation control.

Nature 2017 12 27;552(7683):126-131. Epub 2017 Nov 27.

The Gurdon Institute and Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK.

N-methyladenosine (mA) is an abundant internal RNA modification in both coding and non-coding RNAs that is catalysed by the METTL3-METTL14 methyltransferase complex. However, the specific role of these enzymes in cancer is still largely unknown. Here we define a pathway that is specific for METTL3 and is implicated in the maintenance of a leukaemic state. We identify METTL3 as an essential gene for growth of acute myeloid leukaemia cells in two distinct genetic screens. Downregulation of METTL3 results in cell cycle arrest, differentiation of leukaemic cells and failure to establish leukaemia in immunodeficient mice. We show that METTL3, independently of METTL14, associates with chromatin and localizes to the transcriptional start sites of active genes. The vast majority of these genes have the CAATT-box binding protein CEBPZ present at the transcriptional start site, and this is required for recruitment of METTL3 to chromatin. Promoter-bound METTL3 induces mA modification within the coding region of the associated mRNA transcript, and enhances its translation by relieving ribosome stalling. We show that genes regulated by METTL3 in this way are necessary for acute myeloid leukaemia. Together, these data define METTL3 as a regulator of a chromatin-based pathway that is necessary for maintenance of the leukaemic state and identify this enzyme as a potential therapeutic target for acute myeloid leukaemia.
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http://dx.doi.org/10.1038/nature24678DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6217924PMC
December 2017

Discovery of I-BRD9, a Selective Cell Active Chemical Probe for Bromodomain Containing Protein 9 Inhibition.

J Med Chem 2016 Feb 30;59(4):1425-39. Epub 2015 Apr 30.

Epinova Discovery Performance Unit, GlaxoSmithKline R&D , Stevenage, Hertfordshire SG1 2NY, U.K.

Acetylation of histone lysine residues is one of the most well-studied post-translational modifications of chromatin, selectively recognized by bromodomain "reader" modules. Inhibitors of the bromodomain and extra terminal domain (BET) family of bromodomains have shown profound anticancer and anti-inflammatory properties, generating much interest in targeting other bromodomain-containing proteins for disease treatment. Herein, we report the discovery of I-BRD9, the first selective cellular chemical probe for bromodomain-containing protein 9 (BRD9). I-BRD9 was identified through structure-based design, leading to greater than 700-fold selectivity over the BET family and 200-fold over the highly homologous bromodomain-containing protein 7 (BRD7). I-BRD9 was used to identify genes regulated by BRD9 in Kasumi-1 cells involved in oncology and immune response pathways and to the best of our knowledge, represents the first selective tool compound available to elucidate the cellular phenotype of BRD9 bromodomain inhibition.
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http://dx.doi.org/10.1021/acs.jmedchem.5b00256DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7354103PMC
February 2016

The non-coding snRNA 7SK controls transcriptional termination, poising, and bidirectionality in embryonic stem cells.

Genome Biol 2013 ;14(9):R98

Background: Pluripotency is characterized by a unique transcriptional state, in which lineage-specification genes are poised for transcription upon exposure to appropriate stimuli, via a bivalency mechanism involving the simultaneous presence of activating and repressive methylation marks at promoter-associated histones. Recent evidence suggests that other mechanisms, such as RNA polymerase II pausing, might be operational in this process, but their regulation remains poorly understood.

Results: Here we identify the non-coding snRNA 7SK as a multifaceted regulator of transcription in embryonic stem cells. We find that 7SK represses a specific cohort of transcriptionally poised genes with bivalent or activating chromatin marks in these cells, suggesting a novel poising mechanism independent of Polycomb activity. Genome-wide analysis shows that 7SK also prevents transcription downstream of polyadenylation sites at several active genes, indicating that 7SK is required for normal transcriptional termination or control of 3′-UTR length. In addition, 7SK suppresses divergent upstream antisense transcription at more than 2,600 loci, including many that encode divergent long non-coding RNAs, a finding that implicates the 7SK snRNA in the control of transcriptional bidirectionality.

Conclusions: Our study indicates that a single non-coding RNA, the snRNA 7SK, is a gatekeeper of transcriptional termination and bidirectional transcription in embryonic stem cells and mediates transcriptional poising through a mechanism independent of chromatin bivalency.
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http://dx.doi.org/10.1186/gb-2013-14-9-r98DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4053805PMC
January 2015

Human RNA methyltransferase BCDIN3D regulates microRNA processing.

Cell 2012 Oct;151(2):278-88

Wellcome Trust/Cancer Research UK Gurdon Institute, The Henry Wellcome Building of Cancer and Developmental Biology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK.

MicroRNAs (miRNAs) regulate key biological processes and their aberrant expression may lead to cancer. The primary transcript of canonical miRNAs is sequentially cleaved by the RNase III enzymes, Drosha and Dicer, which generate 5' monophosphate ends that are important for subsequent miRNA functions. In particular, the recognition of the 5' monophosphate of pre-miRNAs by Dicer is important for precise and effective biogenesis of miRNAs. Here, we identify a RNA-methyltransferase, BCDIN3D, that O-methylates this 5' monophosphate and negatively regulates miRNA maturation. Specifically, we show that BCDIN3D phospho-dimethylates pre-miR-145 both in vitro and in vivo and that phospho-dimethylated pre-miR-145 displays reduced processing by Dicer in vitro. Consistently, BCDIN3D depletion leads to lower pre-miR-145 and concomitantly increased mature miR-145 levels in breast cancer cells, which suppresses their tumorigenic phenotypes. Together, our results uncover a miRNA methylation pathway potentially involved in cancer that antagonizes the Dicer-dependent processing of miR-145 as well as other miRNAs.
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http://dx.doi.org/10.1016/j.cell.2012.08.041DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3640255PMC
October 2012

Three distinct patterns of histone H3Y41 phosphorylation mark active genes.

Cell Rep 2012 Sep 20;2(3):470-7. Epub 2012 Sep 20.

Gurdon Institute and Department of Pathology, Cambridge, UK.

The JAK2 tyrosine kinase is a critical mediator of cytokine-induced signaling. It plays a role in the nucleus, where it regulates transcription by phosphorylating histone H3 at tyrosine 41 (H3Y41ph). We used chromatin immunoprecipitation coupled to massively parallel DNA sequencing (ChIP-seq) to define the genome-wide pattern of H3Y41ph in human erythroid leukemia cells. Our results indicate that H3Y41ph is located at three distinct sites: (1) at a subset of active promoters, where it overlaps with H3K4me3, (2) at distal cis-regulatory elements, where it coincides with the binding of STAT5, and (3) throughout the transcribed regions of active, tissue-specific hematopoietic genes. Together, these data extend our understanding of this conserved and essential signaling pathway and provide insight into the mechanisms by which extracellular stimuli may lead to the coordinated regulation of transcription.
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http://dx.doi.org/10.1016/j.celrep.2012.08.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3607218PMC
September 2012

Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia.

Nature 2011 Oct 2;478(7370):529-33. Epub 2011 Oct 2.

Department of Haematology, Cambridge Institute for Medical Research and Addenbrookes Hospital, University of Cambridge, Cambridge CB2 0XY, UK.

Recurrent chromosomal translocations involving the mixed lineage leukaemia (MLL) gene initiate aggressive forms of leukaemia, which are often refractory to conventional therapies. Many MLL-fusion partners are members of the super elongation complex (SEC), a critical regulator of transcriptional elongation, suggesting that aberrant control of this process has an important role in leukaemia induction. Here we use a global proteomic strategy to demonstrate that MLL fusions, as part of SEC and the polymerase-associated factor complex (PAFc), are associated with the BET family of acetyl-lysine recognizing, chromatin 'adaptor' proteins. These data provided the basis for therapeutic intervention in MLL-fusion leukaemia, via the displacement of the BET family of proteins from chromatin. We show that a novel small molecule inhibitor of the BET family, GSK1210151A (I-BET151), has profound efficacy against human and murine MLL-fusion leukaemic cell lines, through the induction of early cell cycle arrest and apoptosis. I-BET151 treatment in two human leukaemia cell lines with different MLL fusions alters the expression of a common set of genes whose function may account for these phenotypic changes. The mode of action of I-BET151 is, at least in part, due to the inhibition of transcription at key genes (BCL2, C-MYC and CDK6) through the displacement of BRD3/4, PAFc and SEC components from chromatin. In vivo studies indicate that I-BET151 has significant therapeutic value, providing survival benefit in two distinct mouse models of murine MLL-AF9 and human MLL-AF4 leukaemia. Finally, the efficacy of I-BET151 against human leukaemia stem cells is demonstrated, providing further evidence of its potent therapeutic potential. These findings establish the displacement of BET proteins from chromatin as a promising epigenetic therapy for these aggressive leukaemias.
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http://dx.doi.org/10.1038/nature10509DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3679520PMC
October 2011

Deciphering c-MYC-regulated genes in two distinct tissues.

BMC Genomics 2011 Sep 30;12:476. Epub 2011 Sep 30.

Wellcome Trust/Cancer Research UK Gurdon Institute, Cambridge, CB2 1QN, UK.

Background: The transcription factor MYC is a critical regulator of diverse cellular processes, including both replication and apoptosis. Differences in MYC-regulated gene expression responsible for such opposing outcomes in vivo remain obscure. To address this we have examined time-dependent changes in global gene expression in two transgenic mouse models in which MYC activation, in either skin suprabasal keratinocytes or pancreatic islet β-cells, promotes tissue expansion or involution, respectively.

Results: Consistent with observed phenotypes, expression of cell cycle genes is increased in both models (albeit enriched in β-cells), as are those involved in cell growth and metabolism, while expression of genes involved in cell differentiation is down-regulated. However, in β-cells, which unlike suprabasal keratinocytes undergo prominent apoptosis from 24 hours, there is up-regulation of genes associated with DNA-damage response and intrinsic apoptotic pathways, including Atr, Arf, Bax and Cycs. In striking contrast, this is not the case for suprabasal keratinocytes, where pro-apoptotic genes such as Noxa are down-regulated and key anti-apoptotic pathways (such as Igf1-Akt) and those promoting angiogenesis are up-regulated. Moreover, dramatic up-regulation of steroid hormone-regulated Kallikrein serine protease family members in suprabasal keratinocytes alone could further enhance local Igf1 actions, such as through proteolysis of Igf1 binding proteins.

Conclusions: Activation of MYC causes cell growth, loss of differentiation and cell cycle entry in both β-cells and suprabasal keratinocytes in vivo. Apoptosis, which is confined to β-cells, may involve a combination of a DNA-damage response and downstream activation of pro-apoptotic signalling pathways, including Cdc2a and p19(Arf)/p53, and downstream targets. Conversely, avoidance of apoptosis in suprabasal keratinocytes may result primarily from the activation of key anti-apoptotic signalling pathways, particularly Igf1-Akt, and induction of an angiogenic response, though intrinsic resistance to induction of p19(Arf) by MYC in suprabasal keratinocytes may contribute.
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http://dx.doi.org/10.1186/1471-2164-12-476DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3206520PMC
September 2011

Nucleosome-interacting proteins regulated by DNA and histone methylation.

Cell 2010 Oct;143(3):470-84

The Gurdon Institute, Department of Pathology, Cambridge, UK.

Modifications on histones or on DNA recruit proteins that regulate chromatin function. Here, we use nucleosomes methylated on DNA and on histone H3 in an affinity assay, in conjunction with a SILAC-based proteomic analysis, to identify "crosstalk" between these two distinct classes of modification. Our analysis reveals proteins whose binding to nucleosomes is regulated by methylation of CpGs, H3K4, H3K9, and H3K27 or a combination thereof. We identify the origin recognition complex (ORC), including LRWD1 as a subunit, to be a methylation-sensitive nucleosome interactor that is recruited cooperatively by DNA and histone methylation. Other interactors, such as the lysine demethylase Fbxl11/KDM2A, recognize nucleosomes methylated on histones, but their recruitment is disrupted by DNA methylation. These data establish SILAC nucleosome affinity purifications (SNAP) as a tool for studying the dynamics between different chromatin modifications and provide a modification binding "profile" for proteins regulated by DNA and histone methylation.
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http://dx.doi.org/10.1016/j.cell.2010.10.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3640253PMC
October 2010