Scientific reports, 2018-11, Vol.8 (1), p.17348-15, Article 17348
2018
Details
- Autor(en) / Beteiligte
- Titel
- DNA methylation dynamics during embryonic development and postnatal maturation of the mouse auditory sensory epithelium
- Ist Teil von
- Scientific reports, 2018-11, Vol.8 (1), p.17348-15, Article 17348
- Ort / Verlag
- England: Nature Publishing Group
- Erscheinungsjahr
- 2018
- Link zum Volltext
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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). Our single-nucleotide resolution maps revealed variations in both general characteristics and dynamics of DNA methylation over time. This allowed us to predict the location of non-coding regulatory regions and to identify several novel candidate regulatory factors, such as Bach2, that connect stage-specific regulatory elements to molecular features that drive the development and maturation of the SE. Constructing in silico regulatory networks around sites of differential methylation enabled us to link key inner ear regulators, such as Atoh1 and Stat3, to pathways responsible for cell lineage determination and maturation, such as the Notch pathway. We also discovered that a putative enhancer, defined as a low methylated region (LMR), can upregulate the GJB6 gene and a neighboring non-coding RNA. The study of inner ear SE methylomes revealed novel regulatory regions in the hearing organ, which may improve diagnostic capabilities, and has the potential to guide the development of therapeutics for hearing loss by providing multiple intervention points for manipulation of the auditory system.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 2045-2322eISSN: 2045-2322DOI: 10.1038/s41598-018-35587-xTitel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6255903
- Format
- –
- Schlagworte
- Animals, Animals, Newborn, Auditory system, Basic Helix-Loop-Helix Transcription Factors - genetics, Basic Helix-Loop-Helix Transcription Factors - metabolism, Basic-Leucine Zipper Transcription Factors - genetics, Basic-Leucine Zipper Transcription Factors - metabolism, Bisulfite, Cell lineage, Connexin 30 - genetics, Deafness, Deafness - genetics, DNA methylation, DNA Methylation - physiology, Drug development, Ear, Inner - cytology, Ear, Inner - embryology, Ear, Inner - growth & development, Embryogenesis, Enhancer Elements, Genetic, Epithelium - embryology, Epithelium - growth & development, Female, Gene Expression Regulation, Developmental, Gene mapping, Genomes, GJB6 protein, Hearing loss, Humans, Hypoxia-Inducible Factor 1, alpha Subunit - genetics, Inner ear, Math1 protein, Maturation, Mice, Inbred C57BL, Nerve Tissue Proteins - genetics, Non-coding RNA, POU Domain Factors - genetics, Pregnancy, Regulatory sequences, Sensory epithelium, Stat3 protein, STAT3 Transcription Factor - genetics, STAT3 Transcription Factor - metabolism