Mattia Pelizzola

Mattia Pelizzola
Istituto Italiano di Tecnologia | IIT · Center for Genomic Science

About

79
Publications
14,342
Reads
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10,542
Citations
Additional affiliations
May 2011 - present
Istituto Italiano di Tecnologia
Position
  • Group Leader
Description
  • http://genomics.iit.it/research/epigenomics-and-transcriptional-regulation
January 2009 - February 2011
Salk Institute for Biological Studies
Position
  • PostDoc Position
January 2007 - January 2009
Yale University
Position
  • PostDoc Position
Education
October 2003 - December 2006
Università degli Studi di Torino
Field of study
  • Computational Biology
October 2002 - May 2003
Università degli Studi di Milano-Bicocca
Field of study
  • Bioinformatics
September 1996 - April 2001
Università degli Studi di Milano-Bicocca
Field of study
  • Industrial Biotechnology

Publications

Publications (79)
Article
Full-text available
The covalent modification of RNA molecules is a pervasive feature of all classes of RNAs and has fundamental roles in the regulation of several cellular processes. Mapping the location of RNA modifications transcriptome-wide is key to unveiling their role and dynamic behaviour, but technical limitations have often hampered these efforts. Nanopore d...
Article
Full-text available
Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm caused by the presence of tyrosine kinase BCR-ABL1 fusion protein, which deregulate transcription and mRNA translation. Tyrosine kinase inhibitors (TKIs) are the first-choice treatment. However, resistance to TKIs remains a challenge to cure CML patients. Here, we reveal that the m6A m...
Chapter
The field of transcriptional regulation generally assumes that changes in transcripts levels reflect changes in transcriptional status of the corresponding gene. While this assumption might hold true for a large population of transcripts, a considerable and still unrecognized fraction of the variation might involve other steps of the RNA lifecycle,...
Article
Full-text available
Despite gene expression programs being notoriously complex, RNA abundance is usually assumed as a proxy for transcriptional activity. Recently developed approaches, able to disentangle transcriptional and post-transcriptional regulatory processes, have revealed a more complex scenario. It is now possible to work out how synthesis, processing and de...
Article
Full-text available
Post-transcriptional repression of gene expression by miRNAs occurs through transcript destabilization or translation inhibition. mRNA decay is known to account for most miRNA-dependent repression. However, because transcript decay occurs co-translationally, whether target translation is a requirement for miRNA-dependent transcript destabilization...
Article
The quantification of the kinetic rates of RNA synthesis, processing, and degradation are largely based on the integrative analysis of total and nascent transcription, the latter being quantified through RNA metabolic labeling. We developed INSPEcT-, a computational method based on the mathematical modeling of premature and mature RNA expression th...
Article
Full-text available
The abundance of RNA species and their response to perturbations are set by the kinetics rates of RNA synthesis, processing, and degradation. However, the visualization, interpretation, and manipulation of these data require familiarity with mathematical modeling and command line tools. INSPEcT-GUI is an R-Shiny interface that allows researchers wi...
Article
N 6-methyladenosine (m 6 A) is one of the most widely studied epigenetic modifications, which plays an important role in many biological processes, such as splicing, RNA localization, and degradation. Studies have shown that m 6 A on lncRNA has important functions, including regulating the expression and functions of lncRNA, regulating the synthesi...
Article
Full-text available
It has been known for a few decades that transcripts can be marked by dozens of different modifications. Yet, we are just at the beginning of charting these marks and understanding their functional impact. High-quality methods were developed for the profiling of some of these marks, and approaches to finely study their impact on specific phases of...
Preprint
Full-text available
Posttranscriptional repression by microRNA (miRNA) occurs through transcript destabilization or translation inhibition. Whereas RNA degradation explains most miRNA-dependent repression, transcript decay occurs co-translationally, raising questions regarding the requirement of target translation to miRNA-dependent transcript destabilization. To asse...
Article
Full-text available
Public repositories of large-scale omics datasets represent a valuable resource for researchers. In fact, data re-analysis can either answer novel questions or provide critical data able to complement in-house experiments. However, despite the development of standards for the compilation of metadata, the identification and organization of samples s...
Article
Full-text available
The histone demethylase LSD1 is a key chromatin regulator that is often deregulated in cancer. Its ortholog, dLsd1 plays a crucial role in Drosophila oogenesis; however, our knowledge of dLsd1 function is insufficient to explain its role in the ovary. Here, we have performed genome-wide analysis of dLsd1 binding in the ovary, and we document that d...
Article
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Satellite cells (SCs) are muscle stem cells that remain quiescent during homeostasis and are activated in response to acute muscle damage or in chronic degenerative conditions such as Duchenne Muscular Dystrophy. The activity of SCs is supported by specialized cells which either reside in the muscle or are recruited in regenerating skeletal muscles...
Article
Upon activation, lymphocytes exit quiescence and undergo substantial increases in cell size, accompanied by activation of energy-producing and anabolic pathways, widespread chromatin decompaction, and elevated transcriptional activity. These changes depend upon prior induction of the Myc transcription factor, but how Myc controls them remains uncle...
Article
Full-text available
Background Covalent RNA modifications, such as N-6-methyladenosine (m⁶A), have been associated with various biological processes, but their role in cancer remains largely unexplored. m⁶A dynamics depends on specific enzymes whose deregulation may also impact in tumorigenesis. Herein, we assessed the differential abundance of m⁶A, its writer VIRMA a...
Preprint
Upon activation, lymphocytes exit quiescence and undergo substantial increases in cell size, accompanied by activation of energy-producing and anabolic pathways, widespread chromatin decompaction and elevated transcriptional activity. These changes depend upon prior induction of the Myc transcription factor, but how Myc controls them remains unclea...
Preprint
Full-text available
The kinetic rates of RNA synthesis, processing and degradation determine the dynamics of transcriptional regulation by governing both the abundance and the responsiveness to modulations of premature and mature RNA species. The study of RNA dynamics is largely based on the integrative analysis of total and nascent transcription, with the latter bein...
Article
Full-text available
N6-methyladenosine (m6A) is the most abundant RNA modification. It has been involved in the regulation of RNA metabolism, including degradation and translation, in both physiological and disease conditions. A recent study showed that m6A-mediated degradation of key transcripts also plays a role in the control of T cells homeostasis and IL-7 induced...
Article
Full-text available
Abstract The inner ear is a complex structure responsible for hearing and balance, and organ pathology is associated with deafness and balance disorders. To evaluate the role of epigenomic dynamics, we performed whole genome bisulfite sequencing at key time points during the development and maturation of the mouse inner ear sensory epithelium (SE)....
Conference Paper
Background & Objective: Epitranscriptomics is a growing new field in Science. RNA modifications, such as N-6-methyladenosine (m6A), play a role in various biological processes but their role in cancer remains largely unexplored.We aimed to assess the value of these epimarkers in a cohort of Testicular Germ Cell Tumours (TGCTs). Method: In silico an...
Article
Full-text available
The genetic alphabet consists of the four letters: C, A, G, and T in DNA and C,A,G, and U in RNA. Triplets of these four letters jointly encode 20 different amino acids out of which proteins of all organisms are built. This system is universal and is found in all kingdoms of life. However, bases in DNA and RNA can be chemically modified. In DNA, ar...
Preprint
Full-text available
Background The mammalian inner ear is a complex morphological structure responsible for hearing and balance, and its pathology is associated with deafness and balance disorders. To evaluate the role of epigenomic dynamics in the development and maturation of mouse inner ear sensory epithelium, we performed whole-genome bisulfite sequencing on inner...
Chapter
Full-text available
DNA methylation profiling in the epigenome of Arabidopsis thaliana (Arabidopsis) has provided great insights in the role of this epigenetic mark for the regulation of transcription in plants, and is often based on high-throughput sequencing. The analysis of these data involves a series of steps including quality checks, filtering, alignment, identi...
Article
Overexpression of the MYC transcription factor causes its widespread interaction with regulatory elements in the genome but leads to the up- and down-regulation of discrete sets of genes. The molecular determinants of these selective transcriptional responses remain elusive. Here, we present an integrated time-course analysis of transcription and m...
Article
Full-text available
Widespread genome hypo-methylation and promoter hyper-methylation of epithelium-specific genes are hallmarks of stable epithelial-to-mesenchymal transition (EMT), which in prostate cancer (PCa) correlates with castration resistance, cancer stem cells generation, chemoresistance and worst prognosis. Exploiting our consolidated 'ex-vivo' system, we s...
Chapter
Epigenetics is particularly relevant in driving cellular differentiation, controlling tissue-specific transcriptional programs, determining imprinting and X chromosome inactivation, and can be altered in diseases. During social interaction tests, mice investigate each other primarily by sniffing their anogenital region, their head, or the rest of t...
Article
Pervasive transcription of the human genome results in a heterogeneous mix of coding RNAs and long noncoding RNAs (lncRNAs). Only a small fraction of lncRNAs have demonstrated regulatory functions, thus making functional lncRNAs difficult to distinguish from nonfunctional transcriptional byproducts. This difficulty has resulted in numerous competin...
Preprint
The pervasive transcription of the human genome results in a heterogeneous mix of coding and long non-coding RNAs (lncRNAs). Only a small fraction of lncRNAs possess demonstrated regulatory functions, making it difficult to distinguish functional lncRNAs from non-functional transcriptional byproducts. This has resulted in numerous competing classif...
Article
Full-text available
Inhibition of bromodomain and extraterminal motif (BET) proteins such as BRD4 bears great promise for cancer treatment and its efficacy has been frequently attributed to Myc downregulation. Here, we use B-cell tumors as a model to address the mechanism of action of JQ1, a widely used BET inhibitor. Although JQ1 led to widespread eviction of BRD4 fr...
Article
Full-text available
Public repositories of large-scale biological data currently contain hundreds of thousands of experiments, including high-throughput sequencing and microarray data. The potential of using these resources to assemble data sets combining samples previously not associated is vastly unexplored. This requires the ability to associate samples with clear...
Article
Full-text available
Next-generation sequencing (NGS) technologies have deeply changed our understanding of cellular processes by delivering an astonishing amount of data at affordable prices; nowadays, many biology laboratories have already accumulated a large number of sequenced samples. However, managing and analyzing these data poses new challenges, which may easil...
Article
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The increasing availability of resequencing data has led to a better understanding of the most important genes in cancer development. Nevertheless, the mutational landscape of many tumor types is heterogeneous and encompasses a long tail of potential driver genes that are systematically excluded by currently available methods due to the low frequen...
Article
Full-text available
The regulation of miRNAs is critical to the definition of cell identity and behavior in normal physiology and disease. To date, the dynamics of miRNA degradation and the mechanisms involved in remain largely obscure, in particular, in higher organisms. Here, we developed a pulse-chase approach based on metabolic RNA labeling to calculate miRNA deca...
Article
Upon recruitment to active enhancers and promoters, RNA polymerase II (Pol II) generates short non-coding transcripts of unclear function. The mechanisms that control the length and the amount of ncRNAs generated by cis-regulatory elements are largely unknown. Here, we show that the adaptor protein WDR82 and its associated complexes actively limit...
Article
Full-text available
Background Numerous methods are available to profile several epigenetic marks, providing data with different genome coverage and resolution. Large epigenomic datasets are then generated, and often combined with other high-throughput data, including RNA-seq, ChIP-seq for transcription factors (TFs) binding and DNase-seq experiments. Despite the nume...
Article
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The gene expression programs regulated by the Myc transcription factor were evaluated by integrated genome-wide profiling of Myc binding sites, chromatin marks and RNA expression in several biological models. Our results indicate that Myc directly drives selective transcriptional regulation, which in certain physiological conditions may indirectly...
Article
Full-text available
Cellular mRNA levels originate from the combined action of multiple regulatory processes, which can be recapitulated by the rates of pre-mRNA synthesis, pre-mRNA processing, and mRNA degradation. Recent experimental and computational advances set the basis to study these intertwined levels of regulation. Nevertheless, software for the comprehensive...
Article
Full-text available
A multi-layered set of epigenetic marks, including post-translational modifications of histones and methylation of DNA, is finely tuned to define the epigenetic state of chromatin in any given cell type under specific conditions. Recently, the knowledge about the combinations of epigenetic marks occurring in the genome of different cell types under...
Article
Full-text available
The c-myc proto-oncogene product, Myc, is a transcription factor that binds thousands of genomic loci 1 . Recent work suggested that rather than up-and downregulating selected groups of genes 1–3 , Myc targets all active promoters and enhancers in the genome (a phenomenon termed 'invasion') and acts as a general amplifier of transcription 4,5 . How...
Article
Full-text available
Understanding the links between genetic, epigenetic and non-genetic factors throughout the lifespan and across generations and their role in disease susceptibility and disease progression offer entirely new avenues and solutions to major problems in our society. To overcome the numerous challenges, we have come up with nine major conclusions to set...
Article
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A key challenge in the analysis of cancer genomes is the identification of driver genes from the vast number of mutations present in a cohort of patients. DOTS-Finder is a new tool that allows the detection of driver genes through the sequential application of functional and frequentist approaches, and is specifically tailored to the analysis of fe...
Article
Full-text available
Both diffusible factors acting in trans and chromatin components acting in cis are implicated in gene regulation, but the extent to which either process causally determines a cell's transcriptional identity is unclear. We recently used cell fusion to define a class of silent genes termed "cis-silenced" (or "occluded") genes, which remain silent eve...
Article
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The gaseous plant hormone ethylene regulates a multitude of growth and developmental processes. How the numerous growth control pathways are coordinated by the ethylene transcriptional response remains elusive. We characterized the dynamic ethylene transcriptional response by identifying targets of the master regulator of the ethylene signaling pat...
Article
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Natural epigenetic variation provides a source for the generation of phenotypic diversity, but to understand its contribution to such diversity, its interaction with genetic variation requires further investigation. Here we report population-wide DNA sequencing of genomes, transcriptomes and methylomes of wild Arabidopsis thaliana accessions. Singl...
Article
Full-text available
Regulation of gene expression by DNA methylation is crucial for defining cellular identities and coordinating organism-wide developmental programs in many organisms. In plants, modulation of DNA methylation in response to environmental conditions represents a potentially robust mechanism to regulate gene expression networks; however, examples of dy...
Article
Full-text available
While genetic mutation is a hallmark of cancer, many cancers also acquire epigenetic alterations during tumorigenesis including aberrant DNA hypermethylation of tumor suppressors, as well as changes in chromatin modifications as caused by genetic mutations of the chromatin-modifying machinery. However, the extent of epigenetic alterations in cancer...
Article
DNA methylation is an important and potentially heritable component of the epigenetic machinery that has a major role in the control of gene expression and can be deregulated in many diseases. This modification of genomic DNA can be assessed using the methylated DNA immunoprecipitation (MeDIP) method, based on the quantification of methylated DNA f...
Article
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Parthenogenetic embryonic stem cells (pESCs) have been generated in several mammalian species from parthenogenetic embryos that would otherwise die around mid-gestation. However, previous reports suggest that pESCs derived from in vivo ovulated (IVO) mature oocytes show limited pluripotency, as evidenced by low chimera production, high tissue prefe...
Article
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Induced pluripotent stem cells (iPSCs) offer immense potential for regenerative medicine and studies of disease and development. Somatic cell reprogramming involves epigenomic reconfiguration, conferring iPSCs with characteristics similar to embryonic stem (ES) cells. However, it remains unknown how complete the reestablishment of ES-cell-like DNA...
Article
Methylation of cytosines is a pervasive feature of eukaryotic genomes and an important epigenetic layer that is fundamental for cellular differentiation processes and control of transcriptional potential. DNA methylation patterns can be inherited and influenced by the environment, diet and aging, and disrupted in diseases. Complete DNA methylomes f...
Article
Full-text available
Analysis of DNA methylation patterns relies increasingly on sequencing-based profiling methods. The four most frequently used sequencing-based technologies are the bisulfite-based methods MethylC-seq and reduced representation bisulfite sequencing (RRBS), and the enrichment-based techniques methylated DNA immunoprecipitation sequencing (MeDIP-seq)...
Article
Human embryonic stem cells (hESCs) share an identical genome with lineage-committed cells, yet possess the remarkable properties of self-renewal and pluripotency. The diverse cellular properties in different cells have been attributed to their distinct epigenomes, but how much epigenomes differ remains unclear. Here, we report that epigenomic lands...
Article
Full-text available
DNA cytosine methylation is a central epigenetic modification that has essential roles in cellular processes including genome regulation, development and disease. Here we present the first genome-wide, single-base-resolution maps of methylated cytosines in a mammalian genome, from both human embryonic stem cells and fetal fibroblasts, along with co...