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1.
Genes Dev ; 28(2): 99-114, 2014 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-24449267

RESUMO

Cellular senescence is a stress response that accompanies stable exit from the cell cycle. Classically, senescence, particularly in human cells, involves the p53 and p16/Rb pathways, and often both of these tumor suppressor pathways need to be abrogated to bypass senescence. In parallel, a number of effector mechanisms of senescence have been identified and characterized. These studies suggest that senescence is a collective phenotype of these multiple effectors, and their intensity and combination can be different depending on triggers and cell types, conferring a complex and diverse nature to senescence. Series of studies on senescence-associated secretory phenotype (SASP) in particular have revealed various layers of functionality of senescent cells in vivo. Here we discuss some key features of senescence effectors and attempt to functionally link them when it is possible.


Assuntos
Senescência Celular/fisiologia , Animais , Núcleo Celular/metabolismo , Senescência Celular/genética , Cromatina/metabolismo , Regulação da Expressão Gênica , Humanos
2.
EMBO Rep ; 20(1)2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30429208

RESUMO

Hypoxia-inducible factor (HIF) is the major transcriptional regulator of cellular responses to hypoxia. The two principal HIF-α isoforms, HIF-1α and HIF-2α, are progressively stabilized in response to hypoxia and form heterodimers with HIF-1ß to activate a broad range of transcriptional responses. Here, we report on the pan-genomic distribution of isoform-specific HIF binding in response to hypoxia of varying severity and duration, and in response to genetic ablation of each HIF-α isoform. Our findings reveal that, despite an identical consensus recognition sequence in DNA, each HIF heterodimer loads progressively at a distinct repertoire of cell-type-specific sites across the genome, with little evidence of redistribution under any of the conditions examined. Marked biases towards promoter-proximal binding of HIF-1 and promoter-distant binding of HIF-2 were observed under all conditions and were consistent in multiple cell type. The findings imply that each HIF isoform has an inherent property that determines its binding distribution across the genome, which might be exploited to therapeutically target the specific transcriptional output of each isoform independently.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Hipóxia Celular/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Transcrição Gênica , Linhagem Celular , Cromatina/genética , DNA/genética , Proteínas de Ligação a DNA/genética , Epigenômica , Regulação da Expressão Gênica/genética , Humanos , Regiões Promotoras Genéticas , Isoformas de Proteínas/genética
3.
Genes Dev ; 27(16): 1800-8, 2013 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-23964094

RESUMO

Senescence is a stress-responsive form of stable cell cycle exit. Senescent cells have a distinct gene expression profile, which is often accompanied by the spatial redistribution of heterochromatin into senescence-associated heterochromatic foci (SAHFs). Studying a key component of the nuclear lamina lamin B1 (LMNB1), we report dynamic alterations in its genomic profile and their implications for SAHF formation and gene regulation during senescence. Genome-wide mapping reveals that LMNB1 is depleted during senescence, preferentially from the central regions of lamina-associated domains (LADs), which are enriched for Lys9 trimethylation on histone H3 (H3K9me3). LMNB1 knockdown facilitates the spatial relocalization of perinuclear H3K9me3-positive heterochromatin, thus promoting SAHF formation, which could be inhibited by ectopic LMNB1 expression. Furthermore, despite the global reduction in LMNB1 protein levels, LMNB1 binding increases during senescence in a small subset of gene-rich regions where H3K27me3 also increases and gene expression becomes repressed. These results suggest that LMNB1 may contribute to senescence in at least two ways due to its uneven genome-wide redistribution: first, through the spatial reorganization of chromatin and, second, through gene repression.


Assuntos
Senescência Celular/genética , Montagem e Desmontagem da Cromatina/genética , Heterocromatina/metabolismo , Lamina Tipo B/metabolismo , Linhagem Celular , Núcleo Celular/metabolismo , Células Cultivadas , Regulação da Expressão Gênica , Heterocromatina/química , Histonas/metabolismo , Lamina Tipo B/genética , Ligação Proteica , Estrutura Terciária de Proteína
4.
Mol Cell ; 47(2): 203-14, 2012 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-22795131

RESUMO

The expansion of repressive epigenetic marks has been implicated in heterochromatin formation during embryonic development, but the general applicability of this mechanism is unclear. Here we show that nuclear rearrangement of repressive histone marks H3K9me3 and H3K27me3 into nonoverlapping structural layers characterizes senescence-associated heterochromatic foci (SAHF) formation in human fibroblasts. However, the global landscape of these repressive marks remains unchanged upon SAHF formation, suggesting that in somatic cells, heterochromatin can be formed through the spatial repositioning of pre-existing repressively marked histones. This model is reinforced by the correlation of presenescent replication timing with both the subsequent layered structure of SAHFs and the global landscape of the repressive marks, allowing us to integrate microscopic and genomic information. Furthermore, modulation of SAHF structure does not affect the occupancy of these repressive marks, nor vice versa. These experiments reveal that high-order heterochromatin formation and epigenetic remodeling of the genome can be discrete events.


Assuntos
Cromatina/química , Heterocromatina/química , Histonas/metabolismo , Bromodesoxiuridina/farmacologia , Senescência Celular , Cromossomos/ultraestrutura , Epigênese Genética , Fibroblastos/citologia , Regulação da Expressão Gênica no Desenvolvimento , Inativação Gênica , Genoma , Estudo de Associação Genômica Ampla , Histonas/química , Humanos , Citometria de Varredura a Laser/métodos , Microscopia de Fluorescência/métodos
5.
PLoS Genet ; 13(7): e1006872, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28715484

RESUMO

Un-physiological activation of hypoxia inducible factor (HIF) is an early event in most renal cell cancers (RCC) following inactivation of the von Hippel-Lindau tumor suppressor. Despite intense study, how this impinges on cancer development is incompletely understood. To test for the impact of genetic signals on this pathway, we aligned human RCC-susceptibility polymorphisms with genome-wide assays of HIF-binding and observed highly significant overlap. Allele-specific assays of HIF binding, chromatin conformation and gene expression together with eQTL analyses in human tumors were applied to mechanistic analysis of one such overlapping site at chromosome 12p12.1. This defined a novel stage-specific mechanism in which the risk polymorphism, rs12814794, directly creates a new HIF-binding site that mediates HIF-1α isoform specific upregulation of its target BHLHE41. The alignment of multiple sites in the HIF cis-acting apparatus with RCC-susceptibility polymorphisms strongly supports a causal model in which minor variation in this pathway exerts significant effects on RCC development.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Carcinoma de Células Renais/genética , Regulação Neoplásica da Expressão Gênica , Predisposição Genética para Doença , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Polimorfismo de Nucleotídeo Único , Alelos , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Carcinoma de Células Renais/diagnóstico , Linhagem Celular Tumoral , Imunoprecipitação da Cromatina , Cromossomos Humanos Par 12/genética , Ciclina D1 , Estudo de Associação Genômica Ampla , Células HeLa , Células Hep G2 , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Células MCF-7 , Locos de Características Quantitativas , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Regulação para Cima
6.
EMBO Rep ; 17(10): 1410-1421, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27506891

RESUMO

Hypoxia-inducible factor (HIF) directs an extensive transcriptional cascade that transduces numerous adaptive responses to hypoxia. Pan-genomic analyses, using chromatin immunoprecipitation and transcript profiling, have revealed large numbers of HIF-binding sites that are generally associated with hypoxia-inducible transcripts, even over long chromosomal distances. However, these studies do not define the specific targets of HIF-binding sites and do not reveal how induction of HIF affects chromatin conformation over distantly connected functional elements. To address these questions, we deployed a recently developed chromosome conformation assay that enables simultaneous high-resolution analyses from multiple viewpoints. These assays defined specific long-range interactions between intergenic HIF-binding regions and one or more promoters of hypoxia-inducible genes, revealing the existence of multiple enhancer-promoter, promoter-enhancer, and enhancer-enhancer interactions. However, neither short-term activation of HIF by hypoxia, nor long-term stabilization of HIF in von Hippel-Lindau (VHL)-defective cells greatly alters these interactions, indicating that at least under these conditions, HIF can operate on preexisting patterns of chromatin-chromatin interactions that define potential transcriptional targets and permit rapid gene activation by hypoxic stress.


Assuntos
Sítios de Ligação , Cromatina/genética , Cromatina/metabolismo , Biologia Computacional/métodos , Fator 1 Induzível por Hipóxia/metabolismo , Regiões Promotoras Genéticas , Algoritmos , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Linhagem Celular Tumoral , Imunoprecipitação da Cromatina , Análise por Conglomerados , Elementos Facilitadores Genéticos , Regulação da Expressão Gênica , Glicólise , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Especificidade de Órgãos/genética , Ligação Proteica , Ativação Transcricional
7.
Bioinformatics ; 29(21): 2699-704, 2013 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-23990411

RESUMO

MOTIVATION: Multiple sequence alignments (MSAs) are usually scored under the assumption that the sequences being aligned have evolved by common descent. Consequently, the differences between sequences reflect the impact of insertions, deletions and mutations. However, non-coding DNA binding sequences, such as transcription factor binding sites (TFBSs), are frequently not related by common descent, and so the existing alignment scoring methods are not well suited for aligning such sequences. RESULTS: We present a novel multiple MSA methodology that scores TFBS DNA sequences by including the interdependence of neighboring bases. We introduced two variants supported by different underlying null hypotheses, one statistically and the other thermodynamically generated. We assessed the alignments through their performance in TFBS prediction; both methods show considerable improvements when compared with standard MSA algorithms. Moreover, the thermodynamically generated null hypothesis outperforms the statistical one due to improved stability in the base stacking free energy of the alignment. The thermodynamically generated null hypothesis method can be downloaded from http://sourceforge.net/projects/msa-edna/. CONTACT: dov.stekel@nottingham.ac.uk. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.


Assuntos
Alinhamento de Sequência/métodos , Análise de Sequência de DNA/métodos , Fatores de Transcrição/metabolismo , Algoritmos , Sítios de Ligação , Interpretação Estatística de Dados , Software , Termodinâmica
8.
J Ment Health ; 23(1): 4-8, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24484185

RESUMO

BACKGROUND: Government strategy for mental health places tackling stigma as a main priority. National initiatives have attempted to tackle stigma by challenging negative media reporting and the use of stereotyped representations of mental illness, with mixed results. Educational interventions have attempted to address stigmatising attitudes in young people but no studies have explored the value of such interventions for film students. AIMS: The study aimed to assess the value of a lecture-based training intervention designed to improve the knowledge and attitudes of student filmmakers towards mental illness and its cinematic representation. METHOD: A self-report questionnaire was administered before and after the intervention, which measured the knowledge and attitudes of the subjects. RESULTS: 32 out of 54 students (59.3%) showed statistically significant improvement in attitudes and knowledge overall, although this was less marked in responses to the attitudinal subset questions compared with knowledge-based questions. Feedback was positive. CONCLUSIONS: The training session was successful in its aims for most but not all students. The intervention is reproducible but further work needs to be done to clarify how best to influence attitudes and behaviour as well as knowledge.


Assuntos
Atitude , Transtornos Mentais/psicologia , Filmes Cinematográficos , Estigma Social , Educação , Humanos , Autorrelato , Estudantes , Inquéritos e Questionários
9.
Br J Haematol ; 159(5): 589-98, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23025544

RESUMO

NKG2D (KLRK1) is an activating receptor on natural killer (NK) and T-cells and binds a diverse panel of polymorphic ligands encoded by the MIC and RAET1 gene families. We studied the clinical importance of retinoic acid early transcript-1 (RAET1) polymorphism in allogeneic stem cell transplantation (SCT) by determining the frequency of 18 single nucleotide polymorphisms (SNPs) and individual RAET1 alleles in 371 patient-donor pairs and relating this to clinical outcome. A strong association was observed between the presence of five SNPs within the patient RAET1L (ULBP6) gene and relapse-free survival and overall survival. Two common alleles of RAET1L were determined and the presence of the protective RAET1L*02 allele in the patient was associated with a relapse-free survival of 44% at 8 years compared with just 25% in patients who lacked a RAET1L*02 allele (P < 0·001). Overall survival at this time was 55% in those with RAET1L*02 allele compared to 39% in patients who lacked a RAET1L*02 allele (P = 0·003). These novel findings indicate a critical role for NKG2D-RAET1L interactions in determining SCT clinical outcome and show RAET1L may have an important influence on regulating the strength of the alloreactive immune response. The data will be of value in guiding the development of future transplant therapy protocols.


Assuntos
Neoplasias Hematológicas/genética , Neoplasias Hematológicas/cirurgia , Transplante de Células-Tronco Hematopoéticas/métodos , Proteínas de Membrana/genética , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Genótipo , Neoplasias Hematológicas/metabolismo , Humanos , Lactente , Recém-Nascido , Leucemia/genética , Leucemia/cirurgia , Ligantes , Linfoma não Hodgkin/genética , Linfoma não Hodgkin/cirurgia , Masculino , Proteínas de Membrana/metabolismo , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/genética , Síndromes Mielodisplásicas/cirurgia , Subfamília K de Receptores Semelhantes a Lectina de Células NK/genética , Subfamília K de Receptores Semelhantes a Lectina de Células NK/metabolismo , Transplante Homólogo , Resultado do Tratamento , Adulto Jovem
10.
Nucleic Acids Res ; 38(12): e135, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20439311

RESUMO

Prediction of transcription factor binding sites is an important challenge in genome analysis. The advent of next generation genome sequencing technologies makes the development of effective computational approaches particularly imperative. We have developed a novel training-based methodology intended for prokaryotic transcription factor binding site prediction. Our methodology extends existing models by taking into account base interdependencies between neighbouring positions using conditional probabilities and includes genomic background weighting. This has been tested against other existing and novel methodologies including position-specific weight matrices, first-order Hidden Markov Models and joint probability models. We have also tested the use of gapped and ungapped alignments and the inclusion or exclusion of background weighting. We show that our best method enhances binding site prediction for all of the 22 Escherichia coli transcription factors with at least 20 known binding sites, with many showing substantial improvements. We highlight the advantage of using block alignments of binding sites over gapped alignments to capture neighbouring position interdependencies. We also show that combining these methods with ChIP-on-chip data has the potential to further improve binding site prediction. Finally we have developed the ungapped likelihood under positional background platform: a user friendly website that gives access to the prediction method devised in this work.


Assuntos
Genômica/métodos , Elementos Reguladores de Transcrição , Fatores de Transcrição/metabolismo , Proteínas de Bactérias/metabolismo , Pareamento de Bases , Sítios de Ligação , Imunoprecipitação da Cromatina , DNA/química , Internet , Análise de Sequência com Séries de Oligonucleotídeos
11.
Sci Rep ; 9(1): 18768, 2019 12 10.
Artigo em Inglês | MEDLINE | ID: mdl-31822727

RESUMO

Emerging evidence suggests that dysregulation of oncogenic pathways requires precise tuning in order for cancer to develop. To test this, we examined the overlap between cis-acting elements of the hypoxia-inducible factor (HIF) pathway and cancer-susceptibility polymorphisms as defined in genome-wide association studies (GWAS). In renal cancer, where HIF is constitutively and un-physiologically activated by mutation of the von Hippel-Lindau tumour suppressor, we observed marked excess overlap, which extended to potential susceptibility polymorphisms that are below the conventional threshold applied in GWAS. In contrast, in other cancers where HIF is upregulated by different mechanisms, including micro-environmental hypoxia, we observed no excess in overlap. Our findings support a 'pathway tuning' model of cancer, whereby precise modulation of multiple outputs of specific, activated pathways is important in oncogenesis. This implies that selective pressures to modulate such pathways operate during cancer development and should focus attempts to identify their nature and consequences.


Assuntos
Carcinogênese/genética , Carcinoma de Células Renais/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Renais/genética , Transdução de Sinais/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Carcinoma de Células Renais/patologia , Linhagem Celular Tumoral , Conjuntos de Dados como Assunto , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Fator 1 Induzível por Hipóxia/genética , Fator 1 Induzível por Hipóxia/metabolismo , Neoplasias Renais/patologia , Mutação , Polimorfismo de Nucleotídeo Único , Proteína Supressora de Tumor Von Hippel-Lindau/genética , Proteína Supressora de Tumor Von Hippel-Lindau/metabolismo
12.
Nat Commun ; 7: 13183, 2016 10 24.
Artigo em Inglês | MEDLINE | ID: mdl-27774982

RESUMO

Clear cell renal cell carcinoma (ccRCC) is characterized by loss of function of the von Hippel-Lindau tumour suppressor (VHL) and unrestrained activation of hypoxia-inducible transcription factors (HIFs). Genetic and epigenetic determinants have an impact on HIF pathways. A recent genome-wide association study on renal cancer susceptibility identified single-nucleotide polymorphisms (SNPs) in an intergenic region located between the oncogenes MYC and PVT1. Here using assays of chromatin conformation, allele-specific chromatin immunoprecipitation and genome editing, we show that HIF binding to this regulatory element is necessary to trans-activate MYC and PVT1 expression specifically in cells of renal tubular origins. Moreover, we demonstrate that the risk-associated polymorphisms increase chromatin accessibility and activity as well as HIF binding to the enhancer. These findings provide further evidence that genetic variation at HIF-binding sites modulates the oncogenic transcriptional output of the VHL-HIF axis and provide a functional explanation for the disease-associated effects of SNPs in ccRCC.


Assuntos
Translocador Nuclear Receptor Aril Hidrocarboneto/genética , Carcinoma de Células Renais/genética , Regulação Neoplásica da Expressão Gênica , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Neoplasias Renais/genética , Polimorfismo de Nucleotídeo Único , Proteínas Proto-Oncogênicas c-myc/genética , Translocador Nuclear Receptor Aril Hidrocarboneto/metabolismo , Sítios de Ligação , Carcinoma de Células Renais/metabolismo , Carcinoma de Células Renais/patologia , Cromatina/química , Cromatina/metabolismo , Imunoprecipitação da Cromatina , Cromossomos Humanos Par 8 , DNA Intergênico/genética , DNA Intergênico/metabolismo , Elementos Facilitadores Genéticos , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Neoplasias Renais/metabolismo , Neoplasias Renais/patologia , Ligação Proteica , Proteínas Proto-Oncogênicas c-myc/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Transdução de Sinais , Proteína Supressora de Tumor Von Hippel-Lindau/genética , Proteína Supressora de Tumor Von Hippel-Lindau/metabolismo
13.
Nat Cell Biol ; 18(9): 979-92, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27525720

RESUMO

Senescence, a persistent form of cell-cycle arrest, is often associated with a diverse secretome, which provides complex functionality for senescent cells within the tissue microenvironment. We show that oncogene-induced senescence is accompanied by a dynamic fluctuation of NOTCH1 activity, which drives a TGF-ß-rich secretome, while suppressing the senescence-associated pro-inflammatory secretome through inhibition of C/EBPß. NOTCH1 and NOTCH1-driven TGF-ß contribute to 'lateral induction of senescence' through a juxtacrine NOTCH-JAG1 pathway. In addition, NOTCH1 inhibition during senescence facilitates upregulation of pro-inflammatory cytokines, promoting lymphocyte recruitment and senescence surveillance in vivo. As enforced activation of NOTCH1 signalling confers a near mutually exclusive secretory profile compared with typical senescence, our data collectively indicate that the dynamic alteration of NOTCH1 activity during senescence dictates a functional balance between these two distinct secretomes: one representing TGF-ß and the other pro-inflammatory cytokines, highlighting that NOTCH1 is a temporospatial controller of secretome composition.


Assuntos
Pontos de Checagem do Ciclo Celular/fisiologia , Receptor Notch1/metabolismo , Animais , Linhagem Celular Tumoral , Senescência Celular , Humanos , Camundongos Transgênicos , Receptor Notch1/genética , Fator de Crescimento Transformador beta/metabolismo
14.
PLoS One ; 10(8): e0134645, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26262842

RESUMO

General activation of hypoxia-inducible factor (HIF) pathways is classically associated with adverse prognosis in cancer and has been proposed to contribute to oncogenic drive. In clear cell renal carcinoma (CCRC) HIF pathways are upregulated by inactivation of the von-Hippel-Lindau tumor suppressor. However HIF-1α and HIF-2α have contrasting effects on experimental tumor progression. To better understand this paradox we examined pan-genomic patterns of HIF DNA binding and associated gene expression in response to manipulation of HIF-1α and HIF-2α and related the findings to CCRC prognosis. Our findings reveal distinct pan-genomic organization of canonical and non-canonical HIF isoform-specific DNA binding at thousands of sites. Overall associations were observed between HIF-1α-specific binding, and genes associated with favorable prognosis and between HIF-2α-specific binding and adverse prognosis. However within each isoform-specific set, individual gene associations were heterogeneous in sign and magnitude, suggesting that activation of each HIF-α isoform contributes a highly complex mix of pro- and anti-tumorigenic effects.


Assuntos
Hipóxia/metabolismo , Neoplasias Renais/metabolismo , Transdução de Sinais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Sítios de Ligação , Linhagem Celular Tumoral , Expressão Gênica , Humanos , Fator 1 Induzível por Hipóxia/genética , Fator 1 Induzível por Hipóxia/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Neoplasias Renais/genética , Neoplasias Renais/mortalidade , Prognóstico , Ligação Proteica , Domínios e Motivos de Interação entre Proteínas , Ativação Transcricional
15.
Front Genet ; 5: 75, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24782889

RESUMO

With the advent of ChIP-seq multiplexing technologies and the subsequent increase in ChIP-seq throughput, the development of working standards for the quality assessment of ChIP-seq studies has received significant attention. The ENCODE consortium's large scale analysis of transcription factor binding and epigenetic marks as well as concordant work on ChIP-seq by other laboratories has established a new generation of ChIP-seq quality control measures. The use of these metrics alongside common processing steps has however not been evaluated. In this study, we investigate the effects of blacklisting and removal of duplicated reads on established metrics of ChIP-seq quality and show that the interpretation of these metrics is highly dependent on the ChIP-seq preprocessing steps applied. Further to this we perform the first investigation of the use of these metrics for ChIP-exo data and make recommendations for the adaptation of the NSC statistic to allow for the assessment of ChIP-exo efficiency.

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