5-Hydroxymethylation marks a class of neuronal gene regulated by intragenic methylcytosine levels.

Rachelle E Irwin, Avinash Thakur, Karla M O'Neill, Colum P Walsh

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Abstract

We recently identified a class of neuronal gene inheriting high levels of intragenic methylation from the mother and maintaining this through later development. We show here that these genes are implicated in basic neuronal functions such as post-synaptic signalling, rather than neuronal development and inherit high levels of 5mC, but not 5hmC, from the mother. 5mC is distributed across the gene body and appears to facilitate transcription, as transcription is reduced in DNA methyltransferase I (Dnmt1) knockout embryonic stem cells as well as in fibroblasts treated with a methyltransferase inhibitor. However in adult brain, transcription is more closely associated with a gain in 5hmC, which occurs without a measurable loss of 5mC. These findings add to growing evidence that there may be a role for 5mC in promoting transcription as well as its classical role in gene silencing. Further interrogation of the mechanisms behind the persistence of gametic marks could potentially lead to insights into neurological disorders.
LanguageEnglish
Title of host publicationUnknown Host Publication
Pages212-212
Number of pages1
Volume84
Publication statusAccepted/In press - 4 Sep 2015
Event18th Meeting of the Irish Society of Human Genetics - Dublin City University
Duration: 4 Sep 2015 → …

Conference

Conference18th Meeting of the Irish Society of Human Genetics
Period4/09/15 → …

Fingerprint

Methyltransferases
Genes
Gene Silencing
Embryonic Stem Cells
Nervous System Diseases
Methylation
Fibroblasts
DNA
Brain

Keywords

  • Methylation
  • 5hmC
  • Brain
  • DNMT1

Cite this

Irwin, R. E., Thakur, A., O'Neill, K. M., & Walsh, C. P. (Accepted/In press). 5-Hydroxymethylation marks a class of neuronal gene regulated by intragenic methylcytosine levels. In Unknown Host Publication (Vol. 84, pp. 212-212)
Irwin, Rachelle E ; Thakur, Avinash ; O'Neill, Karla M ; Walsh, Colum P. / 5-Hydroxymethylation marks a class of neuronal gene regulated by intragenic methylcytosine levels. Unknown Host Publication. Vol. 84 2015. pp. 212-212
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Irwin, RE, Thakur, A, O'Neill, KM & Walsh, CP 2015, 5-Hydroxymethylation marks a class of neuronal gene regulated by intragenic methylcytosine levels. in Unknown Host Publication. vol. 84, pp. 212-212, 18th Meeting of the Irish Society of Human Genetics, 4/09/15.

5-Hydroxymethylation marks a class of neuronal gene regulated by intragenic methylcytosine levels. / Irwin, Rachelle E; Thakur, Avinash; O'Neill, Karla M; Walsh, Colum P.

Unknown Host Publication. Vol. 84 2015. p. 212-212.

Research output: Chapter in Book/Report/Conference proceedingConference contribution

TY - GEN

T1 - 5-Hydroxymethylation marks a class of neuronal gene regulated by intragenic methylcytosine levels.

AU - Irwin, Rachelle E

AU - Thakur, Avinash

AU - O'Neill, Karla M

AU - Walsh, Colum P

PY - 2015/9/4

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N2 - We recently identified a class of neuronal gene inheriting high levels of intragenic methylation from the mother and maintaining this through later development. We show here that these genes are implicated in basic neuronal functions such as post-synaptic signalling, rather than neuronal development and inherit high levels of 5mC, but not 5hmC, from the mother. 5mC is distributed across the gene body and appears to facilitate transcription, as transcription is reduced in DNA methyltransferase I (Dnmt1) knockout embryonic stem cells as well as in fibroblasts treated with a methyltransferase inhibitor. However in adult brain, transcription is more closely associated with a gain in 5hmC, which occurs without a measurable loss of 5mC. These findings add to growing evidence that there may be a role for 5mC in promoting transcription as well as its classical role in gene silencing. Further interrogation of the mechanisms behind the persistence of gametic marks could potentially lead to insights into neurological disorders.

AB - We recently identified a class of neuronal gene inheriting high levels of intragenic methylation from the mother and maintaining this through later development. We show here that these genes are implicated in basic neuronal functions such as post-synaptic signalling, rather than neuronal development and inherit high levels of 5mC, but not 5hmC, from the mother. 5mC is distributed across the gene body and appears to facilitate transcription, as transcription is reduced in DNA methyltransferase I (Dnmt1) knockout embryonic stem cells as well as in fibroblasts treated with a methyltransferase inhibitor. However in adult brain, transcription is more closely associated with a gain in 5hmC, which occurs without a measurable loss of 5mC. These findings add to growing evidence that there may be a role for 5mC in promoting transcription as well as its classical role in gene silencing. Further interrogation of the mechanisms behind the persistence of gametic marks could potentially lead to insights into neurological disorders.

KW - Methylation

KW - 5hmC

KW - Brain

KW - DNMT1

M3 - Conference contribution

VL - 84

SP - 212

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BT - Unknown Host Publication

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Irwin RE, Thakur A, O'Neill KM, Walsh CP. 5-Hydroxymethylation marks a class of neuronal gene regulated by intragenic methylcytosine levels. In Unknown Host Publication. Vol. 84. 2015. p. 212-212