Gagliardi, Miriam
(2016)
Integrative analyses of multi-omic data applied to the
study of a rare human disease, the ICF syndrome.
[Tesi di dottorato]
| Tipologia del documento: |
Tesi di dottorato
|
| Lingua: |
English |
| Titolo: |
Integrative analyses of multi-omic data applied to the
study of a rare human disease, the ICF syndrome |
| Autori: |
| Autore | Email |
|---|
| Gagliardi, Miriam | miriam.gagliardi@igb.cnr.it |
|
| Data: |
31 Marzo 2016 |
| Numero di pagine: |
81 |
| Istituzione: |
Università degli Studi di Napoli Federico II |
| Dipartimento: |
Medicina Molecolare e Biotecnologie Mediche |
| Scuola di dottorato: |
Biotecnologie |
| Dottorato: |
Biologia computazionale e bioinformatica |
| Ciclo di dottorato: |
28 |
| Coordinatore del Corso di dottorato: |
| nome | email |
|---|
| Cocozza, Sergio | cocozza@unina.it |
|
| Tutor: |
| nome | email |
|---|
| Matarazzo, Maria Rosaria | [non definito] |
|
| Data: |
31 Marzo 2016 |
| Numero di pagine: |
81 |
| Parole chiave: |
Epigenomics, Transcriptomics, Human diseases |
| Settori scientifico-disciplinari del MIUR: |
Area 05 - Scienze biologiche > BIO/11 - Biologia molecolare |
[error in script]
[error in script]
| Depositato il: |
13 Apr 2016 20:56 |
| Ultima modifica: |
17 Mag 2017 01:00 |
| URI: |
http://www.fedoa.unina.it/id/eprint/11107 |
Abstract
Application of the next-generation sequencing (NGS) technology has transformed epigenetic
studies, generating large datasets that can be analyzed in different ways to answer a
multitude of questions. Data integration is an essential step to understand intricate biological
processes, such as the epigenetic control of gene regulation.
Recent "multi-omic" studies proposed the intriguing possibility that the intragenic DNA
methylation would play a role in processing of transcripts during transcription modulating
the elongation or splicing. Indeed a kinetic model, in which epigenetic modifications affect
the rate of transcriptional elongation, and/or a recruitment model, in which adaptor proteins
bind to epigenetic modifications recruiting splicing factors have been proposed.
Moreover, it was demonstrated that the intragenic methylation in highly transcribed genes is
exclusively dependent on the DNMT3B function.
However, whether a DNMT3B-dependent epigenetic regulatory network modulates exon
usage and transcription of alternative isoforms remains to be determined.
Through a large-scale integrative study we show that human DNMT3B germline mutations
perturb its intragenic methyltransferase activity, affecting the relative abundance of
transcript isoforms in the context of Immunodeficiency, Centromeric instability, Facial
anomalies syndrome type-1 (ICF1). This correlates with changes of H3K4me3 and
H3K27me3 at isoform-specific transcription start sites. Notably, the newly identified
DNMT3B target genes might significantly contribute to ICF1 phenotype.
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