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1.
Int J Mol Sci ; 22(11)2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-34205983

RESUMO

In the human embryo, the genetic program that orchestrates germ cell specification involves the activation of epigenetic and transcriptional mechanisms that make the germline a unique cell population continuously poised between germness and pluripotency. Germ cell tumors, neoplasias originating from fetal or neonatal germ cells, maintain such dichotomy and can adopt either pluripotent features (embryonal carcinomas) or germness features (seminomas) with a wide range of phenotypes in between these histotypes. Here, we review the basic concepts of cell specification, migration and gonadal colonization of human primordial germ cells (hPGCs) highlighting the analogies of transcriptional/epigenetic programs between these two cell types.


Assuntos
Neoplasias Embrionárias de Células Germinativas/genética , Teratoma/genética , Neoplasias Testiculares/genética , Transcrição Genética , Diferenciação Celular/genética , Epigenômica , Células Germinativas/crescimento & desenvolvimento , Células Germinativas/patologia , Gônadas/crescimento & desenvolvimento , Gônadas/patologia , Humanos , Masculino , Neoplasias Embrionárias de Células Germinativas/patologia , Células-Tronco Pluripotentes/citologia , Teratoma/patologia , Neoplasias Testiculares/patologia
2.
Int J Mol Sci ; 22(11)2021 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-34200325

RESUMO

The SARS-CoV-2 infection determines the COVID-19 syndrome characterized, in the worst cases, by severe respiratory distress, pulmonary and cardiac fibrosis, inflammatory cytokine release, and immunosuppression. This condition has led to the death of about 2.15% of the total infected world population so far. Among survivors, the presence of the so-called persistent post-COVID-19 syndrome (PPCS) is a common finding. In COVID-19 survivors, PPCS presents one or more symptoms: fatigue, dyspnea, memory loss, sleep disorders, and difficulty concentrating. In this study, a cohort of 117 COVID-19 survivors (post-COVID-19) and 144 non-infected volunteers (COVID-19-free) was analyzed using pyrosequencing of defined CpG islands previously identified as suitable for biological age determination. The results show a consistent biological age increase in the post-COVID-19 population, determining a DeltaAge acceleration of 10.45 ± 7.29 years (+5.25 years above the range of normality) compared with 3.68 ± 8.17 years for the COVID-19-free population (p < 0.0001). A significant telomere shortening parallels this finding in the post-COVID-19 cohort compared with COVID-19-free subjects (p < 0.0001). Additionally, ACE2 expression was decreased in post-COVID-19 patients, compared with the COVID-19-free population, while DPP-4 did not change. In light of these observations, we hypothesize that some epigenetic alterations are associated with the post-COVID-19 condition, particularly in younger patients (< 60 years).


Assuntos
Envelhecimento/genética , COVID-19/genética , COVID-19/fisiopatologia , Ilhas de CpG , Encurtamento do Telômero , Telômero/metabolismo , Adulto , Idoso , Enzima de Conversão de Angiotensina 2/sangue , Biomarcadores , COVID-19/complicações , COVID-19/etiologia , Metilação de DNA , Dipeptidil Peptidase 4/sangue , Epigenômica , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Interações entre Hospedeiro e Microrganismos , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Sobreviventes
3.
Molecules ; 26(11)2021 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-34200173

RESUMO

Neuropeptides serve as neurohormones and local paracrine regulators that control neural networks regulating behavior, endocrine system and sensorimotor functions. Their expression is characterized by exceptionally restricted profiles. Circuit-specific and adaptive expression of neuropeptide genes may be defined by transcriptional and epigenetic mechanisms controlled by cell type and subtype sequence-specific transcription factors, insulators and silencers. The opioid peptide dynorphins play a critical role in neurological and psychiatric disorders, pain processing and stress, while their mutations cause profound neurodegeneration in the human brain. In this review, we focus on the prodynorphin gene as a model for the in-depth epigenetic and transcriptional analysis of expression of the neuropeptide genes. Prodynorphin studies may provide a framework for analysis of mechanisms relevant for regulation of neuropeptide genes in normal and pathological human brain.


Assuntos
Encéfalo/metabolismo , Encefalinas/genética , Epigênese Genética/genética , Precursores de Proteínas/genética , Transcrição Genética/genética , Analgésicos Opioides/metabolismo , Animais , Epigenômica/métodos , Regulação da Expressão Gênica/genética , Humanos , Neuropeptídeos/genética
4.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 46(6): 620-627, 2021 Jun 28.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-34275931

RESUMO

Drug resistance is the main obstacle in the treatment of many cancers. It is of great clinical significance to study the mechanism of drug resistance and find new targets. Multi-omics mainly includes genomics, epigenomics, transcriptomics, proteomics, metabolomics, and radiomics. In recent years, the research of tumor resistance has made rapid development, which has significantly accelerated the discovery of new targets.


Assuntos
Genômica , Neoplasias , Epigenômica , Humanos , Metabolômica , Neoplasias/genética , Proteômica , Tecnologia
5.
Mol Cell ; 81(11): 2272-2274, 2021 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-34087178

RESUMO

Pritykin et al. (2021) establish a comprehensive chromatin atlas of CD8+ T cell dysfunction in chronic viral infection and cancer via analysis of bulk and single-cell ATAC-seq datasets across immune challenges. These results unify the classification scheme and molecular programs driving CD8+ T cell dysfunction across disease settings and will facilitate basic discovery and translational efforts in T cell immunity.


Assuntos
Linfócitos T CD8-Positivos , Neoplasias , Cromatina , Epigênese Genética , Epigenômica , Humanos , Neoplasias/genética
6.
Int J Mol Sci ; 22(9)2021 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-34063061

RESUMO

Diabetic neuropathy (DN), the most common chronic and progressive complication of diabetes mellitus (DM), strongly affects patients' quality of life. DN could be present as peripheral, autonomous or, clinically also relevant, uremic neuropathy. The etiopathogenesis of DN is multifactorial, and genetic components play a role both in its occurrence and clinical course. A number of gene polymorphisms in candidate genes have been assessed as susceptibility factors for DN, and most of them are linked to mechanisms such as reactive oxygen species production, neurovascular impairments and modified protein glycosylation, as well as immunomodulation and inflammation. Different epigenomic mechanisms such as DNA methylation, histone modifications and non-coding RNA action have been studied in DN, which also underline the importance of "metabolic memory" in DN appearance and progression. In this review, we summarize most of the relevant data in the field of genetics and epigenomics of DN, hoping they will become significant for diagnosis, therapy and prevention of DN.


Assuntos
Neuropatias Diabéticas/genética , Epigênese Genética , Epigenômica , Animais , Neuropatias Diabéticas/patologia , Neuropatias Diabéticas/fisiopatologia , Neuropatias Diabéticas/terapia , Predisposição Genética para Doença , Humanos , Inflamação/patologia , Sistema Nervoso Periférico/patologia , Sistema Nervoso Periférico/fisiopatologia
7.
Int J Mol Sci ; 22(10)2021 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-34065586

RESUMO

Depression is a highly prevalent, disabling, and often chronic illness that places substantial burdens on patients, families, healthcare systems, and the economy. A substantial minority of patients are unresponsive to current therapies, so there is an urgent need to develop more broadly effective, accessible, and tolerable therapies. Pharmacological regulation of histone acetylation level has been investigated as one potential clinical strategy. Histone acetylation status is considered a potential diagnostic biomarker for depression, while inhibitors of histone deacetylases (HDACs) have garnered interest as novel therapeutics. This review describes recent advances in our knowledge of histone acetylation status in depression and the therapeutic potential of HDAC inhibitors.


Assuntos
Depressão/genética , Epigênese Genética/genética , Histona Desacetilases/genética , Acetilação/efeitos dos fármacos , Animais , Epigenômica/métodos , Inibidores de Histona Desacetilases/farmacologia , Humanos
8.
BMC Genomics ; 22(1): 446, 2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-34126923

RESUMO

BACKGROUND: The combination of sodium bisulfite treatment with highly-parallel sequencing is a common method for quantifying DNA methylation across the genome. The power to detect between-group differences in DNA methylation using bisulfite-sequencing approaches is influenced by both experimental (e.g. read depth, missing data and sample size) and biological (e.g. mean level of DNA methylation and difference between groups) parameters. There is, however, no consensus about the optimal thresholds for filtering bisulfite sequencing data with implications for the reproducibility of findings in epigenetic epidemiology. RESULTS: We used a large reduced representation bisulfite sequencing (RRBS) dataset to assess the distribution of read depth across DNA methylation sites and the extent of missing data. To investigate how various study variables influence power to identify DNA methylation differences between groups, we developed a framework for simulating bisulfite sequencing data. As expected, sequencing read depth, group size, and the magnitude of DNA methylation difference between groups all impacted upon statistical power. The influence on power was not dependent on one specific parameter, but reflected the combination of study-specific variables. As a resource to the community, we have developed a tool, POWEREDBiSeq, which utilizes our simulation framework to predict study-specific power for the identification of DNAm differences between groups, taking into account user-defined read depth filtering parameters and the minimum sample size per group. CONCLUSIONS: Our data-driven approach highlights the importance of filtering bisulfite-sequencing data by minimum read depth and illustrates how the choice of threshold is influenced by the specific study design and the expected differences between groups being compared. The POWEREDBiSeq tool, which can be applied to different types of bisulfite sequencing data (e.g. RRBS, whole genome bisulfite sequencing (WGBS), targeted bisulfite sequencing and amplicon-based bisulfite sequencing), can help users identify the level of data filtering needed to optimize power and aims to improve the reproducibility of bisulfite sequencing studies.


Assuntos
Metilação de DNA , Sulfitos , Epigenômica , Sequenciamento de Nucleotídeos em Larga Escala , Reprodutibilidade dos Testes , Análise de Sequência de DNA
9.
Nat Cell Biol ; 23(6): 620-630, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34108657

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection often causes severe complications and even death. However, asymptomatic infection has also been reported, highlighting the difference in immune responses among individuals. Here we performed single-cell chromatin accessibility and T cell-receptor analyses of peripheral blood mononuclear cells collected from individuals convalescing from COVID-19 and healthy donors. Chromatin remodelling was observed in both innate and adaptive immune cells in the individuals convalescing from COVID-19. Compared with healthy donors, recovered individuals contained abundant TBET-enriched CD16+ and IRF1-enriched CD14+ monocytes with sequential trained and activated epigenomic states. The B-cell lineage in recovered individuals exhibited an accelerated developmental programme from immature B cells to antibody-producing plasma cells. Finally, an integrated analysis of single-cell T cell-receptor clonality with the chromatin accessibility landscape revealed the expansion of putative SARS-CoV-2-specific CD8+ T cells with epigenomic profiles that promote the differentiation of effector or memory cells. Overall, our data suggest that immune cells of individuals convalescing from COVID-19 exhibit global remodelling of the chromatin accessibility landscape, indicative of the establishment of immunological memory.


Assuntos
COVID-19/genética , Epigênese Genética , Epigenômica , Genes Codificadores dos Receptores de Linfócitos T , Memória Imunológica , Subpopulações de Linfócitos/imunologia , Monócitos/imunologia , SARS-CoV-2/imunologia , Análise de Célula Única , Imunidade Adaptativa , Adolescente , Adulto , Idoso , Linfócitos B/imunologia , Linfócitos B/metabolismo , Linfócitos B/virologia , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Linfócitos T CD8-Positivos/virologia , COVID-19/imunologia , COVID-19/metabolismo , COVID-19/virologia , Estudos de Casos e Controles , Diferenciação Celular , Montagem e Desmontagem da Cromatina , Feminino , Perfilação da Expressão Gênica , Interações Hospedeiro-Patógeno , Humanos , Imunidade Inata , Subpopulações de Linfócitos/metabolismo , Subpopulações de Linfócitos/virologia , Masculino , Pessoa de Meia-Idade , Monócitos/metabolismo , Monócitos/virologia , SARS-CoV-2/patogenicidade , Adulto Jovem
10.
Nat Commun ; 12(1): 3714, 2021 06 17.
Artigo em Inglês | MEDLINE | ID: mdl-34140513

RESUMO

The mechanism behind transgenerational epigenetic inheritance is unclear, particularly through the maternal grandparental line. We previously showed that disruption of folate metabolism in mice by the Mtrr hypomorphic mutation results in transgenerational epigenetic inheritance of congenital malformations. Either maternal grandparent can initiate this phenomenon, which persists for at least four wildtype generations. Here, we use genome-wide approaches to reveal genetic stability in the Mtrr model and genome-wide differential DNA methylation in the germline of Mtrr mutant maternal grandfathers. We observe that, while epigenetic reprogramming occurs, wildtype grandprogeny and great grandprogeny exhibit transcriptional changes that correlate with germline methylation defects. One region encompasses the Hira gene, which is misexpressed in embryos for at least three wildtype generations in a manner that distinguishes Hira transcript expression as a biomarker of maternal phenotypic inheritance.


Assuntos
Proteínas de Ciclo Celular/metabolismo , Metilação de DNA , Ferredoxina-NADP Redutase/genética , Ácido Fólico/metabolismo , Células Germinativas/metabolismo , Chaperonas de Histonas/metabolismo , Padrões de Herança/genética , Herança Materna/genética , Fatores de Transcrição/metabolismo , Animais , Biomarcadores/metabolismo , Proteínas de Ciclo Celular/genética , Embrião de Mamíferos/metabolismo , Epigênese Genética , Epigenômica , Feminino , Ferredoxina-NADP Redutase/metabolismo , Hereditariedade , Chaperonas de Histonas/genética , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Linhagem , Fenótipo , Polimorfismo de Nucleotídeo Único , Espermatozoides/metabolismo , Fatores de Transcrição/genética , Trofoblastos/metabolismo , Sequenciamento Completo do Genoma
11.
Science ; 372(6548): 1263-1264, 2021 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-34140370
12.
Int J Mol Sci ; 22(9)2021 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-34065087

RESUMO

Myeloid malignancy is a broad term encapsulating myeloproliferative neoplasms (MPN), myelodysplastic syndrome (MDS) and acute myeloid leukaemia (AML). Initial studies into genomic profiles of these diseases have shown 2000 somatic mutations prevalent across the spectrum of myeloid blood disorders. Epigenetic mutations are emerging as critical components of disease progression, with mutations in genes controlling chromatin regulation and methylation/acetylation status. Genes such as DNA methyltransferase 3A (DNMT3A), ten eleven translocation methylcytosine dioxygenase 2 (TET2), additional sex combs-like 1 (ASXL1), enhancer of zeste homolog 2 (EZH2) and isocitrate dehydrogenase 1/2 (IDH1/2) show functional impact in disease pathogenesis. In this review we discuss how current knowledge relating to disease progression, mutational profile and therapeutic potential is progressing and increasing understanding of myeloid malignancies.


Assuntos
Epigênese Genética , Regulação da Expressão Gênica , Síndromes Mielodisplásicas/genética , Transtornos Mieloproliferativos/genética , Animais , Biomarcadores , Metilação de DNA , Gerenciamento Clínico , Suscetibilidade a Doenças , Epigenômica/métodos , Perfilação da Expressão Gênica , Histonas/metabolismo , Humanos , Terapia de Alvo Molecular , Síndromes Mielodisplásicas/metabolismo , Síndromes Mielodisplásicas/patologia , Síndromes Mielodisplásicas/terapia , Transtornos Mieloproliferativos/metabolismo , Transtornos Mieloproliferativos/patologia , Transtornos Mieloproliferativos/terapia
13.
Nat Cell Biol ; 23(6): 620-630, 2021 06.
Artigo em Inglês | MEDLINE | ID: covidwho-1263492

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection often causes severe complications and even death. However, asymptomatic infection has also been reported, highlighting the difference in immune responses among individuals. Here we performed single-cell chromatin accessibility and T cell-receptor analyses of peripheral blood mononuclear cells collected from individuals convalescing from COVID-19 and healthy donors. Chromatin remodelling was observed in both innate and adaptive immune cells in the individuals convalescing from COVID-19. Compared with healthy donors, recovered individuals contained abundant TBET-enriched CD16+ and IRF1-enriched CD14+ monocytes with sequential trained and activated epigenomic states. The B-cell lineage in recovered individuals exhibited an accelerated developmental programme from immature B cells to antibody-producing plasma cells. Finally, an integrated analysis of single-cell T cell-receptor clonality with the chromatin accessibility landscape revealed the expansion of putative SARS-CoV-2-specific CD8+ T cells with epigenomic profiles that promote the differentiation of effector or memory cells. Overall, our data suggest that immune cells of individuals convalescing from COVID-19 exhibit global remodelling of the chromatin accessibility landscape, indicative of the establishment of immunological memory.


Assuntos
COVID-19/genética , Epigênese Genética , Epigenômica , Genes Codificadores dos Receptores de Linfócitos T , Memória Imunológica , Subpopulações de Linfócitos/imunologia , Monócitos/imunologia , SARS-CoV-2/imunologia , Análise de Célula Única , Imunidade Adaptativa , Adolescente , Adulto , Idoso , Linfócitos B/imunologia , Linfócitos B/metabolismo , Linfócitos B/virologia , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Linfócitos T CD8-Positivos/virologia , COVID-19/imunologia , COVID-19/metabolismo , COVID-19/virologia , Estudos de Casos e Controles , Diferenciação Celular , Montagem e Desmontagem da Cromatina , Feminino , Perfilação da Expressão Gênica , Interações Hospedeiro-Patógeno , Humanos , Imunidade Inata , Subpopulações de Linfócitos/metabolismo , Subpopulações de Linfócitos/virologia , Masculino , Pessoa de Meia-Idade , Monócitos/metabolismo , Monócitos/virologia , SARS-CoV-2/patogenicidade , Adulto Jovem
14.
Nat Commun ; 12(1): 3628, 2021 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-34131135

RESUMO

We present TensorSignatures, an algorithm to learn mutational signatures jointly across different variant categories and their genomic localisation and properties. The analysis of 2778 primary and 3824 metastatic cancer genomes of the PCAWG consortium and the HMF cohort shows that all signatures operate dynamically in response to genomic states. The analysis pins differential spectra of UV mutagenesis found in active and inactive chromatin to global genome nucleotide excision repair. TensorSignatures accurately characterises transcription-associated mutagenesis in 7 different cancer types. The algorithm also extracts distinct signatures of replication- and double strand break repair-driven mutagenesis by APOBEC3A and 3B with differential numbers and length of mutation clusters. Finally, TensorSignatures reproduces a signature of somatic hypermutation generating highly clustered variants at transcription start sites of active genes in lymphoid leukaemia, distinct from a general and less clustered signature of Polη-driven translesion synthesis found in a broad range of cancer types. In summary, TensorSignatures elucidates complex mutational footprints by characterising their underlying processes with respect to a multitude of genomic variables.


Assuntos
Genômica , Mutação , Neoplasias/genética , Algoritmos , Sequência de Bases , Citidina Desaminase/genética , DNA/genética , Quebras de DNA de Cadeia Dupla , Análise Mutacional de DNA , Reparo do DNA , Replicação do DNA , DNA Polimerase Dirigida por DNA/genética , Epigenômica , Humanos , Antígenos de Histocompatibilidade Menor/genética , Modelos Genéticos , Mutagênese , Proteínas/genética , Transcrição Genética/genética
15.
Nat Commun ; 12(1): 3621, 2021 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-34131149

RESUMO

Chromatin structure and accessibility, and combinatorial binding of transcription factors to regulatory elements in genomic DNA control transcription. Genetic variations in genes encoding histones, epigenetics-related enzymes or modifiers affect chromatin structure/dynamics and result in alterations in gene expression contributing to cancer development or progression. Gliomas are brain tumors frequently associated with epigenetics-related gene deregulation. We perform whole-genome mapping of chromatin accessibility, histone modifications, DNA methylation patterns and transcriptome analysis simultaneously in multiple tumor samples to unravel epigenetic dysfunctions driving gliomagenesis. Based on the results of the integrative analysis of the acquired profiles, we create an atlas of active enhancers and promoters in benign and malignant gliomas. We explore these elements and intersect with Hi-C data to uncover molecular mechanisms instructing gene expression in gliomas.


Assuntos
Cromatina , Glioma/genética , Sequências Reguladoras de Ácido Nucleico , Sítios de Ligação , Neoplasias Encefálicas/genética , Imunoprecipitação da Cromatina , DNA/metabolismo , Metilação de DNA , Proteínas de Ligação a DNA/metabolismo , Proteína Potenciadora do Homólogo 2 de Zeste , Epigênese Genética , Epigenômica , Proteína Forkhead Box M1 , Expressão Gênica , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Glioblastoma , Código das Histonas , Histonas , Humanos , Regiões Promotoras Genéticas , Fatores de Transcrição/metabolismo
16.
Nat Commun ; 12(1): 3892, 2021 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-34162876

RESUMO

The decline of brain function during aging is associated with epigenetic changes, including DNA methylation. Lifestyle interventions can improve brain function during aging, but their influence on age-related epigenetic changes is unknown. Using genome-wide DNA methylation sequencing, we here show that experiencing a stimulus-rich environment counteracts age-related DNA methylation changes in the hippocampal dentate gyrus of mice. Specifically, environmental enrichment prevented the aging-induced CpG hypomethylation at target sites of the methyl-CpG-binding protein Mecp2, which is critical to neuronal function. The genes at which environmental enrichment counteracted aging effects have described roles in neuronal plasticity, neuronal cell communication and adult hippocampal neurogenesis and are dysregulated with age-related cognitive decline in the human brain. Our results highlight the stimulating effects of environmental enrichment on hippocampal plasticity at the level of DNA methylation and give molecular insights into the specific aspects of brain aging that can be counteracted by lifestyle interventions.


Assuntos
Envelhecimento , Ilhas de CpG/genética , Metilação de DNA , Meio Ambiente , Hipocampo/metabolismo , Fatores Etários , Animais , Giro Denteado/metabolismo , Epigenômica/métodos , Feminino , Hipocampo/citologia , Humanos , Camundongos Endogâmicos C57BL , Neurogênese/genética , Plasticidade Neuronal/genética , Neurônios/metabolismo
17.
No Shinkei Geka ; 49(3): 466-475, 2021 May.
Artigo em Japonês | MEDLINE | ID: mdl-34092551

RESUMO

Advances in genetic and epigenetic analyses and immunohistochemical studies involving the development of mutation-specific or histone-methylated antibodies have provided many significant findings about gliomas. Based on these findings, the WHO developed and published the classification of tumors of the central nervous system in 2016. In the classification system, molecular information was combined with pathological findings. After its publication, the Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy-Not Official WHO(cIMAPCT-NOW)was published to evaluate and recommend changes to future central nervous system tumor classifications. This review describes the genetic and epigenetic features of gliomas, mainly those associated with the WHO classification and cIMPACT-NOW.


Assuntos
Neoplasias do Sistema Nervoso Central , Glioma , Epigenômica , Genômica , Glioma/genética , Humanos , Mutação
18.
Int J Mol Sci ; 22(11)2021 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-34072237

RESUMO

In this review, we focus on bioinformatic oncology as an integrative discipline that incorporates knowledge from the mathematical, physical, and computational fields to further the biomedical understanding of cancer. Before providing a deeper insight into the bioinformatics approach and utilities involved in oncology, we must understand what is a system biology framework and the genetic connection, because of the high heterogenicity of the backgrounds of people approaching precision medicine. In fact, it is essential to providing general theoretical information on genomics, epigenomics, and transcriptomics to understand the phases of multi-omics approach. We consider how to create a multi-omics model. In the last section, we describe the new frontiers and future perspectives of this field.


Assuntos
Epigenômica , Genômica , Neoplasias/etiologia , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/imunologia , Transformação Celular Neoplásica/metabolismo , Aberrações Cromossômicas , Biologia Computacional/métodos , Suscetibilidade a Doenças , Epigenômica/métodos , Predisposição Genética para Doença , Genômica/métodos , Humanos , Aprendizado de Máquina , Medicina de Precisão , Proteômica/métodos , Transcriptoma
19.
Int J Mol Sci ; 22(11)2021 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-34063996

RESUMO

Methylation systems have been conserved during the divergence of plants and animals, although they are regulated by different pathways and enzymes. However, studies on the interactions of the epigenomes among evolutionarily distant organisms are lacking. To address this, we studied the epigenetic modification and gene expression of plant chromosome fragments (~30 Mb) in a human-Arabidopsis hybrid cell line. The whole-genome bisulfite sequencing results demonstrated that recombinant Arabidopsis DNA could retain its plant CG methylation levels even without functional plant methyltransferases, indicating that plant DNA methylation states can be maintained even in a different genomic background. The differential methylation analysis showed that the Arabidopsis DNA was undermethylated in the centromeric region and repetitive elements. Several Arabidopsis genes were still expressed, whereas the expression patterns were not related to the gene function. We concluded that the plant DNA did not maintain the original plant epigenomic landscapes and was under the control of the human genome. This study showed how two diverging genomes can coexist and provided insights into epigenetic modifications and their impact on the regulation of gene expressions between plant and animal genomes.


Assuntos
Arabidopsis/genética , Cromossomos de Plantas/genética , Epigênese Genética/genética , Células Híbridas/fisiologia , Linhagem Celular , Metilação de DNA/genética , DNA de Plantas/genética , Epigenoma/genética , Epigenômica/métodos , Genoma de Planta/genética , Humanos , Metiltransferases/genética , Sequências Repetitivas de Ácido Nucleico/genética
20.
Nat Commun ; 12(1): 3337, 2021 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-34099689

RESUMO

Binding of mammalian transcription factors (TFs) to regulatory regions is hindered by chromatin compaction and DNA methylation of their binding sites. Nevertheless, pioneer transcription factors (PFs), a distinct class of TFs, have the ability to access nucleosomal DNA, leading to nucleosome remodelling and enhanced chromatin accessibility. Whether PFs can bind to methylated sites and induce DNA demethylation is largely unknown. Using a highly parallelized approach to investigate PF ability to bind methylated DNA and induce DNA demethylation, we show that the interdependence between DNA methylation and TF binding is more complex than previously thought, even within a select group of TFs displaying pioneering activity; while some PFs do not affect the methylation status of their binding sites, we identified PFs that can protect DNA from methylation and others that can induce DNA demethylation at methylated binding sites. We call the latter super pioneer transcription factors (SPFs), as they are seemingly able to overcome several types of repressive epigenetic marks. Finally, while most SPFs induce TET-dependent active DNA demethylation, SOX2 binding leads to passive demethylation, an activity enhanced by the co-binding of OCT4. This finding suggests that SPFs could interfere with epigenetic memory during DNA replication.


Assuntos
Sítios de Ligação , Metilação de DNA , DNA/metabolismo , Ensaios de Triagem em Larga Escala , Fatores de Transcrição SOXB1/genética , Fatores de Transcrição SOXB1/metabolismo , Animais , Cromatina , Desmetilação do DNA , Replicação do DNA , Epigenômica , Expressão Gênica , Camundongos , Nucleossomos , Fator 3 de Transcrição de Octâmero/metabolismo , Ligação Proteica , RNA Interferente Pequeno/genética , Células Sf9 , Fatores de Transcrição/metabolismo
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