PT  - JOURNAL ARTICLE
AU  - Tslil Gabrieli
AU  - Hila Sharim
AU  - Gil Nifker
AU  - Jonathan Jeffet
AU  - Tamar Shahal
AU  - Rani Arielly
AU  - Michal Levi-Sakin
AU  - Lily Hoch
AU  - Nissim Arbib
AU  - Yael Michaeli
AU  - Yuval Ebenstein
TI  - Genome-wide epigenetic profiling of 5-hydroxymethylcytosine by long-read optical mapping
AID  - 10.1101/260166
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 260166
4099  - http://biorxiv.org/content/early/2018/02/05/260166.short
4100  - http://biorxiv.org/content/early/2018/02/05/260166.full
AB  - The epigenetic mark 5-hydroxymethylcytosine (5-hmC) is a distinct product of active enzymatic demethylation that is linked to gene regulation, development and disease. Genome-wide 5-hmC profiles generated by short-read next-generation sequencing are limited in providing long-range epigenetic information relevant to highly variable genomic regions, such as the 3.7 Mbp disease-related Human Leukocyte Antigen (HLA) region. We present a long-read, single-molecule mapping technology that generates hybrid genetic/epigenetic profiles of native chromosomal DNA. The genome-wide distribution of 5- hmC in human peripheral blood cells correlates well with 5-hmC DNA immunoprecipitation (hMeDIP) sequencing. However, the long read length of 100 kbp-1Mbp produces 5-hmC profiles across variable genomic regions that failed to showup in the sequencing data. In addition, optical 5-hmC mapping shows strong correlation between the 5-hmC density in gene bodies and the corresponding level of gene expression. The single molecule concept provides information on the distribution and coexistence of 5-hmC signals at multiple genomic loci on the same genomic DNA molecule, revealing long-range correlations and cell-to-cell epigenetic variation.