Cell–cell coupling and DNA methylation abnormal phenotypes in the after-hours mice
Abstract Background DNA methylation has emerged as an important epigenetic regulator of brain processes, including circadian rhythms. However, how DNA methylation intervenes between environmental signals, such as light entrainment, and the transcriptional and translational molecular mechanisms of th...
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Series: | Epigenetics & Chromatin |
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doaj-d86afad3f2174d6ea036e7d177eee01c2021-01-10T12:36:16ZengBMCEpigenetics & Chromatin1756-89352021-01-0114111810.1186/s13072-020-00373-5Cell–cell coupling and DNA methylation abnormal phenotypes in the after-hours miceFederico Tinarelli0Elena Ivanova1Ilaria Colombi2Erica Barini3Edoardo Balzani4Celina Garcia Garcia5Laura Gasparini6Michela Chiappalone7Gavin Kelsey8Valter Tucci9Genetics and Epigenetics of Behaviour (GEB) Laboratory, Istituto Italiano Di TecnologiaEpigenetics Programme, The Babraham InstituteNeuroscience and Brain Technologies, Istituto Italiano Di TecnologiaNeurodevelopmental and Neurodegenerative Disease Laboratory, Istituto Italiano Di TecnologiaGenetics and Epigenetics of Behaviour (GEB) Laboratory, Istituto Italiano Di TecnologiaGenetics and Epigenetics of Behaviour (GEB) Laboratory, Istituto Italiano Di TecnologiaNeurodevelopmental and Neurodegenerative Disease Laboratory, Istituto Italiano Di TecnologiaNeuroscience and Brain Technologies, Istituto Italiano Di TecnologiaEpigenetics Programme, The Babraham InstituteGenetics and Epigenetics of Behaviour (GEB) Laboratory, Istituto Italiano Di TecnologiaAbstract Background DNA methylation has emerged as an important epigenetic regulator of brain processes, including circadian rhythms. However, how DNA methylation intervenes between environmental signals, such as light entrainment, and the transcriptional and translational molecular mechanisms of the cellular clock is currently unknown. Here, we studied the after-hours mice, which have a point mutation in the Fbxl3 gene and a lengthened circadian period. Methods In this study, we used a combination of in vivo, ex vivo and in vitro approaches. We measured retinal responses in Afh animals and we have run reduced representation bisulphite sequencing (RRBS), pyrosequencing and gene expression analysis in a variety of brain tissues ex vivo. In vitro, we used primary neuronal cultures combined to micro electrode array (MEA) technology and gene expression. Results We observed functional impairments in mutant neuronal networks, and a reduction in the retinal responses to light-dependent stimuli. We detected abnormalities in the expression of photoreceptive melanopsin (OPN4). Furthermore, we identified alterations in the DNA methylation pathways throughout the retinohypothalamic tract terminals and links between the transcription factor Rev-Erbα and Fbxl3. Conclusions The results of this study, primarily represent a contribution towards an understanding of electrophysiological and molecular phenotypic responses to external stimuli in the Afh model. Moreover, as DNA methylation has recently emerged as a new regulator of neuronal networks with important consequences for circadian behaviour, we discuss the impact of the Afh mutation on the epigenetic landscape of circadian biology.https://doi.org/10.1186/s13072-020-00373-5 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Federico Tinarelli Elena Ivanova Ilaria Colombi Erica Barini Edoardo Balzani Celina Garcia Garcia Laura Gasparini Michela Chiappalone Gavin Kelsey Valter Tucci |
spellingShingle |
Federico Tinarelli Elena Ivanova Ilaria Colombi Erica Barini Edoardo Balzani Celina Garcia Garcia Laura Gasparini Michela Chiappalone Gavin Kelsey Valter Tucci Cell–cell coupling and DNA methylation abnormal phenotypes in the after-hours mice Epigenetics & Chromatin |
author_facet |
Federico Tinarelli Elena Ivanova Ilaria Colombi Erica Barini Edoardo Balzani Celina Garcia Garcia Laura Gasparini Michela Chiappalone Gavin Kelsey Valter Tucci |
author_sort |
Federico Tinarelli |
title |
Cell–cell coupling and DNA methylation abnormal phenotypes in the after-hours mice |
title_short |
Cell–cell coupling and DNA methylation abnormal phenotypes in the after-hours mice |
title_full |
Cell–cell coupling and DNA methylation abnormal phenotypes in the after-hours mice |
title_fullStr |
Cell–cell coupling and DNA methylation abnormal phenotypes in the after-hours mice |
title_full_unstemmed |
Cell–cell coupling and DNA methylation abnormal phenotypes in the after-hours mice |
title_sort |
cell–cell coupling and dna methylation abnormal phenotypes in the after-hours mice |
publisher |
BMC |
series |
Epigenetics & Chromatin |
issn |
1756-8935 |
publishDate |
2021-01-01 |
description |
Abstract Background DNA methylation has emerged as an important epigenetic regulator of brain processes, including circadian rhythms. However, how DNA methylation intervenes between environmental signals, such as light entrainment, and the transcriptional and translational molecular mechanisms of the cellular clock is currently unknown. Here, we studied the after-hours mice, which have a point mutation in the Fbxl3 gene and a lengthened circadian period. Methods In this study, we used a combination of in vivo, ex vivo and in vitro approaches. We measured retinal responses in Afh animals and we have run reduced representation bisulphite sequencing (RRBS), pyrosequencing and gene expression analysis in a variety of brain tissues ex vivo. In vitro, we used primary neuronal cultures combined to micro electrode array (MEA) technology and gene expression. Results We observed functional impairments in mutant neuronal networks, and a reduction in the retinal responses to light-dependent stimuli. We detected abnormalities in the expression of photoreceptive melanopsin (OPN4). Furthermore, we identified alterations in the DNA methylation pathways throughout the retinohypothalamic tract terminals and links between the transcription factor Rev-Erbα and Fbxl3. Conclusions The results of this study, primarily represent a contribution towards an understanding of electrophysiological and molecular phenotypic responses to external stimuli in the Afh model. Moreover, as DNA methylation has recently emerged as a new regulator of neuronal networks with important consequences for circadian behaviour, we discuss the impact of the Afh mutation on the epigenetic landscape of circadian biology. |
url |
https://doi.org/10.1186/s13072-020-00373-5 |
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