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A human tissue map of 5-hydroxymethylcytosines exhibits tissue specificity through gene and enhancer modulation

ABSTRACT: A human tissue map of 5-hydroxymethylcytosines exhibits tissue specificity through gene and enhancer modulation

PROVIDER: PRJNA603959 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR10989800_1.fastq.gz	Fastqsanger.gz
	SRR10989800_2.fastq.gz	Fastqsanger.gz
	SRR10989801_1.fastq.gz	Fastqsanger.gz
	SRR10989801_2.fastq.gz	Fastqsanger.gz
	SRR10989802_1.fastq.gz	Fastqsanger.gz

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A human tissue map of 5-hydroxymethylcytosines exhibits tissue specificity through gene and enhancer modulation

Project description:DNA 5-hydroxymethylcytosine (5hmC) modification is known to be associated with gene transcription and frequently used as a mark to investigate dynamic DNA methylation conversion during mammalian development and in human diseases. However, the lack of genome-wide 5hmC profiles in different human tissue types impedes drawing generalized conclusions about how 5hmC is implicated in transcription activity and tissue specificity. To meet this need, we describe herein, the development of a 5hmC tissue map by characterizing 5hmC genomic distributions in 19 human tissues derived from 10 organ systems. Subsequent sequencing results enabled the identification of genome-wide 5hmC distributions that uniquely separated donor samples by tissue type. Further comparison of 5hmC profiles with transcriptomes and histone modifications revealed that 5hmC was preferentially enriched on tissue-specific gene bodies and enhancers. Taken together, we report herein an extensive 5hmC map across diverse human tissue types and suggest an important role of 5hmC in tissue-specific development by integration with public epigenomic data. This resource will facilitate future studies of DNA demethylation in pathogenesis and development of 5hmC as biomarkers for various human diseases.

2020-10-28 | GSE144530 | GEO

A human tissue map of 5-hydroxymethylcytosines exhibits tissue specificity through gene and enhancer modulation.

Project description:DNA 5-hydroxymethylcytosine (5hmC) modification is known to be associated with gene transcription and frequently used as a mark to investigate dynamic DNA methylation conversion during mammalian development and in human diseases. However, the lack of genome-wide 5hmC profiles in different human tissue types impedes drawing generalized conclusions about how 5hmC is implicated in transcription activity and tissue specificity. To meet this need, we describe the development of a 5hmC tissue map by characterizing the genomic distributions of 5hmC in 19 human tissues derived from ten organ systems. Subsequent sequencing results enabled the identification of genome-wide 5hmC distributions that uniquely separates samples by tissue type. Further comparison of the 5hmC profiles with transcriptomes and histone modifications revealed that 5hmC is preferentially enriched on tissue-specific gene bodies and enhancers. Taken together, the results provide an extensive 5hmC map across diverse human tissue types that suggests a potential role of 5hmC in tissue-specific development; as well as a resource to facilitate future studies of DNA demethylation in pathogenesis and the development of 5hmC as biomarkers.

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Whole-genome analysis of 5-hydroxymethylcytosines and 5-methylcytosines at base resolution in human brain

Project description:5-hydroxymethylcytosines (5hmC) is particularly abundant in mammalian brain with little-known functions. Here we present the first genome-wide and single-base-resolution maps of 5hmC and 5mC in human brain by combined application of TAB-Seq and MethylC-Seq. We report that the majority of modified cytosines are hydroxymethylated in adult human brain, a significant proportion of which are highly-hydroxymethylated with enrichment in active genic regions and distal-regulatory elements. 5hmC is more enriched in poised than active enhancers, and CpG island shores and enhancers show comparable 5hmC profiles. Notably, 5hmC spikes were identified at the 5’ splicing sites, suggesting a link between 5hmC and splicing. Additionally, we identified a transcription-correlated 5hmC bias towards to sense strand and a 5mC bias towards antisense strand of gene bodies, and a bias towards C-rich sequences surrounding the 5hmC sites. Our data imply multiple roles for 5hmC in alternative splicing and gene regulation in addition to be an intermediate of DNA demethylation in human brain. Examination of hydroxymethylomes of 1 adult and 1 fetal brain tissue of frontal lobe, as well as 1 methylome of the same adult.

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