5-hmC in the Brain is Abundant in Synaptic Genes and Shows Differences at the Exon-intron Boundary

Overview

Journal Nat Struct Mol Biol

Specialties Cell Biology
Molecular Biology

Date 2012 Sep 11

PMID 22961382

Citations 141

Authors

Tarang Khare

Shraddha Pai

Karolis Koncevicius

Mrinal Pal

Edita Kriukiene

Zita Liutkeviciute

Manuel Irimia

Peixin Jia

Carolyn Ptak

Menghang Xia

Raymond Tice

Mamoru Tochigi

Solange Morera

Anaies Nazarians

Denise Belsham

Albert H C Wong

Benjamin J Blencowe

Sun Chong Wang

Philipp Kapranov

Rafal Kustra

Viviane Labrie

Saulius Klimasauskas

Arturas Petronis

Affiliations

Soon will be listed here.

Abstract

The 5-methylcytosine (5-mC) derivative 5-hydroxymethylcytosine (5-hmC) is abundant in the brain for unknown reasons. Here we characterize the genomic distribution of 5-hmC and 5-mC in human and mouse tissues. We assayed 5-hmC by using glucosylation coupled with restriction-enzyme digestion and microarray analysis. We detected 5-hmC enrichment in genes with synapse-related functions in both human and mouse brain. We also identified substantial tissue-specific differential distributions of these DNA modifications at the exon-intron boundary in human and mouse. This boundary change was mainly due to 5-hmC in the brain but due to 5-mC in non-neural contexts. This pattern was replicated in multiple independent data sets and with single-molecule sequencing. Moreover, in human frontal cortex, constitutive exons contained higher levels of 5-hmC relative to alternatively spliced exons. Our study suggests a new role for 5-hmC in RNA splicing and synaptic function in the brain.

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