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1.
F1000Res ; 10: 182, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34354812

RESUMO

Background: The vault RNAs (vtRNAs) are a class of 84-141-nt eukaryotic non-coding RNAs transcribed by RNA polymerase III, associated to the ribonucleoprotein complex known as vault particle. Of the four human vtRNA genes, vtRNA1-1, vtRNA1-2 and vtRNA1-3, clustered at locus 1, are integral components of the vault particle, while vtRNA2-1 is a more divergent homologue located in a second locus. Gene expression studies of vtRNAs in large cohorts have been hindered by their unsuccessful sequencing using conventional transcriptomic approaches. Methods: VtRNA expression in The Cancer Genome Atlas (TCGA) Pan-Cancer cohort was estimated using the genome-wide DNA methylation and chromatin accessibility data (ATAC-seq) of their genes as surrogate variables. The association between vtRNA expression and patient clinical outcome, immune subtypes and transcriptionally co-regulated gene programs was analyzed in the dataset. Results: VtRNA1-1 has the most accessible chromatin, followed by vtRNA1-2, vtRNA2-1 and vtRNA1-3. Although the vtRNAs are co-regulated by transcription factors related to viral infection, vtRNA2-1 is the most independently regulated homologue. VtRNA1-1 and vtRNA1-3 chromatin status does not significantly change in cancer tissues. Meanwhile, vtRNA2-1 and vtRNA1-2 expression is widely deregulated in neoplastic tissues and its alteration is compatible with a broad oncogenic role for vtRNA1-2, and both tumor suppressor and oncogenic functions for vtRNA2-1. Yet, vtRNA1-1, vtRNA1-2 and vtRNA2-1 promoter DNA methylation predicts a shorter patient overall survival cancer-wide. In addition, gene ontology analyses of vtRNAs co-regulated genes identify a chromosome regulatory domain, epithelial differentiation, immune and thyroid cancer gene sets for specific vtRNAs. Furthermore, vtRNA expression patterns are associated with cancer immune subtypes and vtRNA1-2 expression is positively associated with cell proliferation and wound healing. Conclusions: Our study presents the landscape of vtRNA expression cancer-wide, identifying co-regulated gene networks and ontological pathways associated with the different vtRNA genes that may account for their diverse roles in cancer.


Assuntos
Cromatina , Neoplasias , Biologia , Cromatina/genética , Metilação de DNA , Humanos , Neoplasias/genética , RNA/metabolismo
2.
Int J Mol Sci ; 22(16)2021 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-34445413

RESUMO

Chromatin 3D structure plays a crucial role in regulation of gene activity. Previous studies have envisioned spatial contact formations between chromatin domains with different epigenetic properties, protein compositions and transcription activity. This leaves specific DNA sequences that affect chromosome interactions. The Drosophila melanogaster polytene chromosomes are involved in non-allelic ectopic pairing. The mutant strain agnts3, a Drosophila model for Williams-Beuren syndrome, has an increased frequency of ectopic contacts (FEC) compared to the wild-type strain Canton-S (CS). Ectopic pairing can be mediated by some specific DNA sequences. In this study, using our Homology Segment Analysis software, we estimated the correlation between FEC and frequency of short matching DNA fragments (FMF) for all sections of the X chromosome of Drosophila CS and agnts3 strains. With fragment lengths of 50 nucleotides (nt), CS showed a specific FEC-FMF correlation for 20% of the sections involved in ectopic contacts. The correlation was unspecific in agnts3, which may indicate the alternative epigenetic mechanisms affecting FEC in the mutant strain. Most of the fragments that specifically contributed to FMF were related to 1.688 or 372-bp middle repeats. Thus, middle repetitive DNA may serve as an organizer of ectopic pairing.


Assuntos
Cromatina/química , DNA Satélite/genética , Drosophila melanogaster/genética , Síndrome de Williams/genética , Cromossomo X/genética , Animais , Pareamento de Bases , Cromatina/genética , Biologia Computacional/métodos , Modelos Animais de Doenças , Humanos , Cromossomos Politênicos/genética , Software
3.
Mol Cell ; 81(15): 3043-3045, 2021 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-34358457

RESUMO

Neguembor et al. (2021) use super-resolution microscopy to illuminate genome packaging inside the cell nucleus. They discover that transcription and topoisomerases protect chromatin from collapsing in a crumpled state refractory to DNA loop extrusion by cohesin proteins.


Assuntos
Proteínas de Ciclo Celular , Proteínas Cromossômicas não Histona , Proteínas de Ciclo Celular/genética , Cromatina/genética , Proteínas Cromossômicas não Histona/genética , DNA/genética , Humanos
4.
Yi Chuan ; 43(8): 758-774, 2021 Aug 20.
Artigo em Chinês | MEDLINE | ID: mdl-34413016

RESUMO

CTCF (CCCTC-binding factor) is a zinc-finger protein which plays a vital role in the three-dimensional (3D) genome architecture. A pair of forward-reverse convergent CTCF binding sites (CBS elements) mediates long-distance DNA interactions to form chromatin loops with the assistance of the cohesin complex, while CBS elements at the chromatin domain boundaries show reverse-forward divergent patterns and function as insulators to discriminate against DNA interaction between chromatin domains. However, there are still many unresolved problems regarding CTCF-mediated insulation function. In order to study the connections between chromatin loops and the insulation function of CBS elements, we combinatorically inverted CBS elements at the HOXD locus by using CRISPR/Cas9 DNA-fragment editing methods in the HEK293T cell line and obtained five different kinds of single-cell CRISPR clones. By performing quantitative high-resolution chromosome conformation capture copy (QHR-4C) experiments, we found that boundary CBS inversions abolish original chromatin loops and establish new loops from the opposite direction, thus shifting the insulator boundary to the new divergent CTCF sites. Furthermore, tandem CBS elements block cohesin permeated from the opposite orientation to function as insulators. RNA-seq experiments showed that alterations of local three-dimensional genome architecture would further influence gene expression of the HOXD cluster. In conclusion, a pair of divergent CBS elements function as insulators by forming chromatin loops within chromatin domains to block cohesin sliding.


Assuntos
Cromatina , Genoma , Sítios de Ligação , Cromatina/genética , DNA , Células HEK293 , Humanos
5.
Yi Chuan ; 43(8): 775-791, 2021 Aug 20.
Artigo em Chinês | MEDLINE | ID: mdl-34413017

RESUMO

The genome architectural protein CTCF (CCCTC-binding factor) not only mediates long-distance chromatin interactions between distal enhancers and target promoters, but also functions as an important insulator-binding factor to block improper enhancer activation of non-target promoters, and is thus of great significance to transcriptional regulation of developmental genes. The Hox (Homeobox) gene family plays an important role in the development of the brain, bones, and limbs. The spatiotemporal colinear expression of the HOXD cluster along the proximal-distal axis of limbs is regulated by two clusters of enhancers known as super-enhancers located in the flanking regulatory regions. We focused on the HOXD cluster to explore the architectural role of CTCF in transcriptional regulation of developmental genes. The HOXD cluster contains 9 paralogous genes intermixed with a series of CBS (CTCF-binding site) elements. Using the CRISPR DNA-fragment editing system, we generated a series of single-cell HEK293T clones with deletion of increasing numbers of reverse CBS elements. RNA-seq experiments revealed decreased levels of HOXD gene expression. In addition, chromosome conformation capture experiments revealed increased long-distance chromatin interactions between HOXD and the upstream enhancer cluster and corresponding decreased interactions between HOXD and the downstream enhancer cluster. Thus, tandem reverse CTCF sites function as insulators to maintain HOXD regulatory balance between the upstream and downstream enhancer clusters. This study has interesting implications on the precise gene expression control of the Hox family during animal development.


Assuntos
Cromatina , Elementos Facilitadores Genéticos , Animais , Cromatina/genética , DNA , Elementos Facilitadores Genéticos/genética , Células HEK293 , Humanos , Regiões Promotoras Genéticas
6.
Methods Mol Biol ; 2351: 41-65, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34382183

RESUMO

Enhancers are transcribed by RNA polymerase II (Pol II). In order to study the regulation of enhancer transcription and its function in target gene control, methods are required that track genome transcription with high precision in vivo. Here, we provide step-by-step guidance for performing native elongating transcript sequencing (NET-Seq) in mammalian cells. NET-Seq allows quantitative measurements of transcription genome-wide, including enhancer transcription, with single-nucleotide and DNA strand resolution. The approach consists of capturing and efficiently converting the 3'-ends of the nascent RNA into a sequencing library followed by next-generation sequencing and computational data analysis. The protocol includes quality control measurements to monitor the success of the main steps. Following this protocol, a NET-Seq library is obtained within 5 days.


Assuntos
Elementos Facilitadores Genéticos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Análise de Sequência de RNA/métodos , Transcrição Genética , Animais , Células Cultivadas , Cromatina/genética , Biologia Computacional/métodos , DNA , Biblioteca Gênica , Humanos , Reação em Cadeia da Polimerase , RNA , RNA Polimerase II/metabolismo , Software
7.
Methods Mol Biol ; 2351: 3-22, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34382181

RESUMO

Knowledge in gene transcription and chromatin regulation has been intensely studied for decades, but thanks to next-generation sequencing (NGS) techniques there has been a major leap forward in the last few years. Historically, identification of specific enhancer elements has led to the identification of master transcription factors (TFs) in the 1990s. Genetic and biochemical experiments have identified the key regulators controlling RNA polymerase II (RNAPII) transcription and structurally analyses have elucidated detailed mechanisms. NGS and the development of chromatin immunoprecipitation (ChIP) have accelerated the gain of knowledge in the recent years. By now, we have a dazzling wealth of techniques that are currently used to put gene expression into a genome-wide context. This book is an attempt to assemble useful protocols for many researchers within and nearby research areas. In general, these innovative techniques focus on enhancer and promoter studies. The techniques should also be of interest for related fields such as DNA repair and replication.


Assuntos
Elementos Facilitadores Genéticos , Regulação da Expressão Gênica , Regiões Promotoras Genéticas , Transcrição Genética , Animais , Sítios de Ligação , Cromatina/genética , Cromatina/metabolismo , Imunoprecipitação da Cromatina , Metilação de DNA , Epigênese Genética , Histonas/metabolismo , Humanos , Ligação Proteica , RNA Polimerase II/metabolismo
8.
Methods Mol Biol ; 2351: 93-104, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34382185

RESUMO

MNase-Seq is a genome-wide procedure that allows mapping of DNA associated to nucleosomes following micrococcal nuclease digestion. It is a rapid and robust technology useful for the analysis of chromatin properties genome-wide at the resolution of mono-nucleosomes. Here, we describe how to produce high-resolution nucleosome maps of cells grown in suspension or adherent mammalian cells. After only three steps: nuclei or cell preparation, native MNase digestion and DNA purification, libraries for high-throughput sequencing can be prepared. Genome-wide nucleosome maps allow analyzing chromatin opening at promoters or enhancers, nucleosome displacement, or labile nucleosome occupancy depending on the digestion condition used. As presented, MNase-Seq is a versatile tool for investigating chromatin dynamics, regulation, and to define open chromatin regions of regulatory elements in mammalian genomes.


Assuntos
Elementos Facilitadores Genéticos , Estudo de Associação Genômica Ampla/métodos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Nucleossomos/metabolismo , Regiões Promotoras Genéticas , Animais , Células Cultivadas , Cromatina/genética , Cromatina/metabolismo , Mapeamento Cromossômico , Biologia Computacional/métodos , Biblioteca Gênica
9.
Methods Mol Biol ; 2351: 105-121, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34382186

RESUMO

Assay for Transposase-Accessible Chromatin using sequencing (ATAC-Seq) is a method to investigate the accessibility of chromatin in a genome-wide fashion. In this chapter, we provide a brief history of the chromatin accessibility field followed by a detailed protocol to perform ATAC-Seq assay.


Assuntos
Montagem e Desmontagem da Cromatina , Cromatina/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Biologia Computacional/métodos , Elementos de DNA Transponíveis , Análise de Dados , Regulação da Expressão Gênica , Biblioteca Gênica , Estudo de Associação Genômica Ampla , Humanos , Nucleossomos/metabolismo , Controle de Qualidade , Análise de Sequência de DNA , Transposases/metabolismo
10.
Methods Mol Biol ; 2351: 123-145, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34382187

RESUMO

The positioning of nucleosomes regulates the accessibility of genomic DNA and can impact the activities of functional elements. Nucleosome positioning is highly consistent at each genomic location in any particular cell-type, but can vary in an orchestrated fashion between different cell-types and between genomic loci according to their activities. Here, we describe a technique-"ChIP-MNase" (chromatin immunoprecipitation linked to micrococcal nuclease mapping)-to determine nucleosome positions at chosen sets of genomic features that can be defined by their molecular composition and recovered by chromatin immunoprecipitation. ChIP-MNase enables high-resolution analysis of nucleosome positioning at genomic regions-of-interest and can allow differential analysis of alleles undergoing distinct molecular processes.


Assuntos
Alelos , Sequenciamento de Cromatina por Imunoprecipitação/métodos , Imunoprecipitação da Cromatina/métodos , Mapeamento Cromossômico/métodos , Loci Gênicos , Nuclease do Micrococo/metabolismo , Nucleossomos/metabolismo , Sítios de Ligação , Células Cultivadas , Cromatina/genética , Cromatina/metabolismo , Montagem e Desmontagem da Cromatina , Ligação Proteica , Controle de Qualidade
11.
Methods Mol Biol ; 2351: 147-161, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34382188

RESUMO

Sequential ChIP (ChIP-reChIP) enables the characterization of the same nucleosome for two different types of modifications or histone subtypes. Here, we describe a ChIP-reChIP protocol to identify a heterotypic (asymmetric) H2A.Z-H2A-containing nucleosome. In this method, following MNase digestion of chromatin to mostly a mononucleosome fraction, H2A.Z-containing nucleosomes are first immunoprecipitated using affinity purified anti-H2A.Z antibodies. This H2A.Z-containing nucleosome fraction is then subsequently immunoprecipitated using anti-H2A affinity purified antibodies to yield an enriched population of heterotypic H2A.Z-H2A containing nucleosomes. This protocol can be adopted to investigate any pair-wise combination of any histone variant, histone posttranslational modification, or any other protein that binds to a modified nucleosome.


Assuntos
Montagem e Desmontagem da Cromatina , Imunoprecipitação da Cromatina/métodos , Cromatina/genética , Cromatina/metabolismo , Nucleossomos/metabolismo , Sítios de Ligação , Histonas/metabolismo , Ligação Proteica
12.
Methods Mol Biol ; 2351: 165-179, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34382189

RESUMO

Targeted chromatin capture (T2C) is a 3C-based method and is used to study the 3D chromatin organization, interactomes and structural changes associated with gene regulation, progression through the cell cycle, and cell survival and development. Low input targeted chromatin capture (low-T2C) is an optimized version of the T2C protocol for low numbers of cells. Here, we describe the protocol for low-T2C, including all experimental steps and bioinformatics tools in detail.


Assuntos
Montagem e Desmontagem da Cromatina , Cromatina/genética , Biologia Computacional/métodos , Cromatina/química , Cromatina/metabolismo , Mapeamento Cromossômico , Regulação da Expressão Gênica , Biblioteca Gênica , Genômica/métodos , Reprodutibilidade dos Testes
13.
Methods Mol Biol ; 2351: 181-199, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34382190

RESUMO

Proximity ligation-assisted ChIP-Seq (PLAC-Seq), also known as HiChIP, is a method to detect and quantify chromatin contacts anchored at genomic regions bound by specific proteins or histone modifications. By combining in situ Hi-C and chromatin immunoprecipitation (ChIP) using antibodies against transcription factors (TFs) or histone marks of interest, the method achieves targeted interrogation of chromatin organization at a subset of genomic regions. PLAC-Seq is able to identify long-range chromatin interactions at kilobase-scale resolution with significantly reduced sequencing cost.


Assuntos
Sequenciamento de Cromatina por Imunoprecipitação/métodos , Cromatina/genética , Sítios de Ligação , Cromatina/metabolismo , Ligação Proteica , Fatores de Transcrição/metabolismo
14.
Methods Mol Biol ; 2351: 201-210, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34382191

RESUMO

Regulation of gene expression is a key feature for higher eukaryotes and how chromatin topology relates to gene activation is an intense area of research. Enhancer-promoter interactions are believed to mediate activation of target genes. Bidirectional transcription represents one hallmark of active enhancers that can be measured using transcriptome technologies such as Cap analysis of gene expression (CAGE). Recently, we have developed RNA and DNA interacting complexes ligated and sequenced (RADICL-Seq) a novel methodology to map genome-wide RNA-chromatin interactions in intact nuclei. Here, we describe how CAGE and RADICL-Seq data can be used to characterize enhancer elements and identify their target genes.


Assuntos
Biologia Computacional/métodos , Elementos Facilitadores Genéticos , Regulação da Expressão Gênica , Regiões Promotoras Genéticas , Capuzes de RNA , Algoritmos , Cromatina/genética , Bases de Dados Genéticas , Sequenciamento de Nucleotídeos em Larga Escala , Sítio de Iniciação de Transcrição , Transcrição Genética , Ativação Transcricional , Transcriptoma
15.
Methods Mol Biol ; 2351: 211-227, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34382192

RESUMO

The open chromatin enrichment and network Hi-C (OCEAN-C) was developed not only for identifying large-scale chromatin structures, including topologically associated domains (TADs) and A/B compartments, but also for globally mapping hubs of open chromatin interactions (HOCIs) and their interaction networks independent of antibody and bait-sequences.


Assuntos
Montagem e Desmontagem da Cromatina , Cromatina/genética , Biologia Computacional/métodos , Sítios de Ligação , Cromatina/metabolismo , Regulação da Expressão Gênica , Biblioteca Gênica , Sequenciamento de Nucleotídeos em Larga Escala , Ligação Proteica , Controle de Qualidade , Software , Transcrição Genética , Navegador
16.
Methods Mol Biol ; 2351: 229-248, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34382193

RESUMO

Chromosome conformation capture and its variants interrogate population-average chromatin structure at a higher resolution and throughput than microscopic methods. Capture Hi-C is a variant tailored for the simultaneous assessment of all interactions with thousands of specific bait sequences, so is particularly suited to genome-wide studies of promoter interactions with distal regulatory elements, such as enhancers. We present the principles and methods for Promoter Capture Hi-C (PCHi-C), from experimental design to data analysis.


Assuntos
Mapeamento Cromossômico/métodos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Regiões Promotoras Genéticas , Sequências Reguladoras de Ácido Nucleico , Cromatina/genética , Cromatina/metabolismo , Cromossomos , Análise de Dados , Elementos Facilitadores Genéticos , Estudo de Associação Genômica Ampla
17.
Methods Mol Biol ; 2351: 251-274, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34382194

RESUMO

In this chapter, we describe the proteomic approach named "Native Chromatin Proteomics" (N-ChroP) that couples a modified Chromatin ImmunoPrecipitation (ChIP) protocol with the mass spectrometry (MS) analysis of immunoprecipitated proteins to study the combinatorial enrichment or exclusion of histone post-translational modifications (PTMs) at specific genomic regions, such as promoters or enhancers. We describe the protocol steps from the digestion of chromatin and nucleosome immunoprecipitation to histone digestion and peptide enrichment prior to MS analysis, up to the MS raw data analysis. We also discuss current challenges and offer suggestions based on the direct hands-on experience acquired during the method setup.


Assuntos
Imunoprecipitação da Cromatina/métodos , Cromatina/genética , Cromatina/metabolismo , Genômica , Histonas/metabolismo , Processamento de Proteína Pós-Traducional , Proteômica , Cromatografia Líquida , Proteínas de Ligação a DNA/metabolismo , Análise de Dados , Genômica/métodos , Nucleossomos/metabolismo , Proteômica/métodos , Espectrometria de Massas em Tandem
18.
Methods Mol Biol ; 2351: 275-288, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34382195

RESUMO

Functionalization of the genome is carried out by proteins that bind to DNA to regulate gene expression. Since this process is highly dynamic, context-dependent, and rarely performed by single proteins alone, we here describe ChIP-SICAP to identify proteins that co-localize with a protein of interest on the genome. Benefiting from its nature as a dual purification approach via ChIP and DNA biotinylation, ChIP-SICAP distinguishes genuine chromatin-binders and is uniquely placed to identify novel players in genome regulation.


Assuntos
Imunoprecipitação da Cromatina/métodos , Cromatina/genética , Cromatina/metabolismo , Proteínas de Ligação a DNA/metabolismo , Sítios de Ligação , Biotinilação , DNA/genética , DNA/metabolismo , Histonas/metabolismo , Espectrometria de Massas , Peptídeo Hidrolases , Ligação Proteica , Proteômica/métodos
19.
Methods Mol Biol ; 2351: 289-303, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34382196

RESUMO

Interactions between regulatory proteins and specific genomic regions are critical for all chromatin-based processes, including transcription, DNA replication, and DNA repair. Genome-wide mapping of such interactions is most commonly performed with chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-Seq), but a number of orthogonal methods employing targeted enzymatic activity have also been introduced. We previously described a genome-wide implementation of chromatin endogenous cleavage (ChEC-Seq), wherein a protein of interest is fused to micrococcal nuclease (MNase) to enable targeted, calcium-dependent genomic cleavage. Here, we describe the ChEC-Seq protocol for use in budding yeast though it can be used in other organisms in conjunction with appropriate methods for introduction of an MNase fusion protein.


Assuntos
Sequenciamento de Cromatina por Imunoprecipitação/métodos , Cromatina/genética , Cromatina/metabolismo , Proteínas de Ligação a DNA/metabolismo , Estudo de Associação Genômica Ampla , Estudo de Associação Genômica Ampla/métodos , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Saccharomycetales/genética , Saccharomycetales/metabolismo
20.
Methods Mol Biol ; 2351: 307-320, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34382197

RESUMO

The transition from silenced heterochromatin to a biologically active state and vice versa is a fundamental part of the implementation of cell type-specific gene expression programs. To reveal structure-function relationships and dissect the underlying mechanisms, experiments that ectopically induce transcription are highly informative. In particular, the approach to perturb chromatin states by recruiting fusions of the catalytically inactive dCas9 protein in a sequence-specific manner to a locus of interest has been used in numerous applications. Here, we describe how this approach can be applied to activate pericentric heterochromatin (PCH) in mouse cells as a prototypic silenced state by providing protocols for the following workflow: (a) Recruitment of dCas9 fusion constructs with the strong transcriptional activator VPR to PCH. (b) Analysis of the resulting changes in chromatin compaction, epigenetic marks, and active transcription by fluorescence microscopy-based readouts. (c) Automated analysis of the resulting images with a set of scripts in the R programming language. Furthermore, we discuss how parameters for chromatin decondensation and active transcription are extracted from these experiments and can be combined with other readouts to gain insights into PCH activation.


Assuntos
Proteína 9 Associada à CRISPR/metabolismo , Regulação da Expressão Gênica , Heterocromatina/genética , Ativação Transcricional , Animais , Proteína 9 Associada à CRISPR/genética , Cromatina/genética , Cromatina/metabolismo , Fibroblastos/metabolismo , Imunofluorescência/métodos , Expressão Gênica , Heterocromatina/metabolismo , Processamento de Imagem Assistida por Computador , Camundongos , Microscopia de Fluorescência , Ligação Proteica , Transfecção , Fluxo de Trabalho
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