Late-replicating heterochromatin is characterized by decreased cytosine methylation in the human genome

Masako Suzuki, Mayumi Oda, María Paz Ramos, Marién Pascual, Kevin Lau, Edyta Stasiek, Frederick Agyiri, Reid Thompson, Jacob L. Glass, Qiang Jing, Richard Sandstrom, Melissa J. Fazzari, R. Scott Hansen, John A. Stamatoyannopoulos, Andrew S. McLellan, John M. Greally

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Heterochromatin is believed to be associated with increased levels of cytosine methylation. With the recent availability of genome-wide, high-resolution molecular data reflecting chromatin organization and methylation, such relationships can be explored systematically. As well-defined surrogates for heterochromatin, we tested the relationship between DNA replication timing and DNase hypersensitivity with cytosine methylation in two human cell types, unexpectedly finding the later-replicating, more heterochromatic regions to be less methylated than early replicating regions. When we integrated gene-expression data into the study, we found that regions of increased gene expression were earlier replicating, as previously identified, and that transcription-targeted cytosine methylation in gene bodies contributes to the positive correlation with early replication. A self-organizing map (SOM) approach was able to identify genomic regions with early replication and increased methylation, but lacking annotated transcripts, loci missed in simple two variable analyses, possibly encoding unrecognized intergenic transcripts. We conclude that the relationship of cytosine methylation with heterochromatin is not simple and depends on whether the genomic context is tandemly repetitive sequences often found near centromeres, which are known to be heterochromatic and methylated, or the remaining majority of the genome, where cytosine methylation is targeted preferentially to the transcriptionally active, euchromatic compartment of the genome.

Original languageEnglish (US)
Pages (from-to)1833-1840
Number of pages8
JournalGenome Research
Volume21
Issue number11
DOIs
StatePublished - Nov 1 2011
Externally publishedYes

Fingerprint

Heterochromatin
Cytosine
Human Genome
Methylation
Genome
DNA Replication Timing
Gene Expression
Deoxyribonucleases
Centromere
Nucleic Acid Repetitive Sequences
Chromatin
Hypersensitivity
Genes

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Suzuki, M., Oda, M., Ramos, M. P., Pascual, M., Lau, K., Stasiek, E., ... Greally, J. M. (2011). Late-replicating heterochromatin is characterized by decreased cytosine methylation in the human genome. Genome Research, 21(11), 1833-1840. https://doi.org/10.1101/gr.116509.110

Late-replicating heterochromatin is characterized by decreased cytosine methylation in the human genome. / Suzuki, Masako; Oda, Mayumi; Ramos, María Paz; Pascual, Marién; Lau, Kevin; Stasiek, Edyta; Agyiri, Frederick; Thompson, Reid; Glass, Jacob L.; Jing, Qiang; Sandstrom, Richard; Fazzari, Melissa J.; Hansen, R. Scott; Stamatoyannopoulos, John A.; McLellan, Andrew S.; Greally, John M.

In: Genome Research, Vol. 21, No. 11, 01.11.2011, p. 1833-1840.

Research output: Contribution to journalArticle

Suzuki, M, Oda, M, Ramos, MP, Pascual, M, Lau, K, Stasiek, E, Agyiri, F, Thompson, R, Glass, JL, Jing, Q, Sandstrom, R, Fazzari, MJ, Hansen, RS, Stamatoyannopoulos, JA, McLellan, AS & Greally, JM 2011, 'Late-replicating heterochromatin is characterized by decreased cytosine methylation in the human genome', Genome Research, vol. 21, no. 11, pp. 1833-1840. https://doi.org/10.1101/gr.116509.110
Suzuki, Masako ; Oda, Mayumi ; Ramos, María Paz ; Pascual, Marién ; Lau, Kevin ; Stasiek, Edyta ; Agyiri, Frederick ; Thompson, Reid ; Glass, Jacob L. ; Jing, Qiang ; Sandstrom, Richard ; Fazzari, Melissa J. ; Hansen, R. Scott ; Stamatoyannopoulos, John A. ; McLellan, Andrew S. ; Greally, John M. / Late-replicating heterochromatin is characterized by decreased cytosine methylation in the human genome. In: Genome Research. 2011 ; Vol. 21, No. 11. pp. 1833-1840.
@article{41438ca884c644b3b4137a084f3ae3ea,
title = "Late-replicating heterochromatin is characterized by decreased cytosine methylation in the human genome",
abstract = "Heterochromatin is believed to be associated with increased levels of cytosine methylation. With the recent availability of genome-wide, high-resolution molecular data reflecting chromatin organization and methylation, such relationships can be explored systematically. As well-defined surrogates for heterochromatin, we tested the relationship between DNA replication timing and DNase hypersensitivity with cytosine methylation in two human cell types, unexpectedly finding the later-replicating, more heterochromatic regions to be less methylated than early replicating regions. When we integrated gene-expression data into the study, we found that regions of increased gene expression were earlier replicating, as previously identified, and that transcription-targeted cytosine methylation in gene bodies contributes to the positive correlation with early replication. A self-organizing map (SOM) approach was able to identify genomic regions with early replication and increased methylation, but lacking annotated transcripts, loci missed in simple two variable analyses, possibly encoding unrecognized intergenic transcripts. We conclude that the relationship of cytosine methylation with heterochromatin is not simple and depends on whether the genomic context is tandemly repetitive sequences often found near centromeres, which are known to be heterochromatic and methylated, or the remaining majority of the genome, where cytosine methylation is targeted preferentially to the transcriptionally active, euchromatic compartment of the genome.",
author = "Masako Suzuki and Mayumi Oda and Ramos, {Mar{\'i}a Paz} and Mari{\'e}n Pascual and Kevin Lau and Edyta Stasiek and Frederick Agyiri and Reid Thompson and Glass, {Jacob L.} and Qiang Jing and Richard Sandstrom and Fazzari, {Melissa J.} and Hansen, {R. Scott} and Stamatoyannopoulos, {John A.} and McLellan, {Andrew S.} and Greally, {John M.}",
year = "2011",
month = "11",
day = "1",
doi = "10.1101/gr.116509.110",
language = "English (US)",
volume = "21",
pages = "1833--1840",
journal = "PCR Methods and Applications",
issn = "1088-9051",
publisher = "Cold Spring Harbor Laboratory Press",
number = "11",

}

TY - JOUR

T1 - Late-replicating heterochromatin is characterized by decreased cytosine methylation in the human genome

AU - Suzuki, Masako

AU - Oda, Mayumi

AU - Ramos, María Paz

AU - Pascual, Marién

AU - Lau, Kevin

AU - Stasiek, Edyta

AU - Agyiri, Frederick

AU - Thompson, Reid

AU - Glass, Jacob L.

AU - Jing, Qiang

AU - Sandstrom, Richard

AU - Fazzari, Melissa J.

AU - Hansen, R. Scott

AU - Stamatoyannopoulos, John A.

AU - McLellan, Andrew S.

AU - Greally, John M.

PY - 2011/11/1

Y1 - 2011/11/1

N2 - Heterochromatin is believed to be associated with increased levels of cytosine methylation. With the recent availability of genome-wide, high-resolution molecular data reflecting chromatin organization and methylation, such relationships can be explored systematically. As well-defined surrogates for heterochromatin, we tested the relationship between DNA replication timing and DNase hypersensitivity with cytosine methylation in two human cell types, unexpectedly finding the later-replicating, more heterochromatic regions to be less methylated than early replicating regions. When we integrated gene-expression data into the study, we found that regions of increased gene expression were earlier replicating, as previously identified, and that transcription-targeted cytosine methylation in gene bodies contributes to the positive correlation with early replication. A self-organizing map (SOM) approach was able to identify genomic regions with early replication and increased methylation, but lacking annotated transcripts, loci missed in simple two variable analyses, possibly encoding unrecognized intergenic transcripts. We conclude that the relationship of cytosine methylation with heterochromatin is not simple and depends on whether the genomic context is tandemly repetitive sequences often found near centromeres, which are known to be heterochromatic and methylated, or the remaining majority of the genome, where cytosine methylation is targeted preferentially to the transcriptionally active, euchromatic compartment of the genome.

AB - Heterochromatin is believed to be associated with increased levels of cytosine methylation. With the recent availability of genome-wide, high-resolution molecular data reflecting chromatin organization and methylation, such relationships can be explored systematically. As well-defined surrogates for heterochromatin, we tested the relationship between DNA replication timing and DNase hypersensitivity with cytosine methylation in two human cell types, unexpectedly finding the later-replicating, more heterochromatic regions to be less methylated than early replicating regions. When we integrated gene-expression data into the study, we found that regions of increased gene expression were earlier replicating, as previously identified, and that transcription-targeted cytosine methylation in gene bodies contributes to the positive correlation with early replication. A self-organizing map (SOM) approach was able to identify genomic regions with early replication and increased methylation, but lacking annotated transcripts, loci missed in simple two variable analyses, possibly encoding unrecognized intergenic transcripts. We conclude that the relationship of cytosine methylation with heterochromatin is not simple and depends on whether the genomic context is tandemly repetitive sequences often found near centromeres, which are known to be heterochromatic and methylated, or the remaining majority of the genome, where cytosine methylation is targeted preferentially to the transcriptionally active, euchromatic compartment of the genome.

UR - http://www.scopus.com/inward/record.url?scp=80555157482&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=80555157482&partnerID=8YFLogxK

U2 - 10.1101/gr.116509.110

DO - 10.1101/gr.116509.110

M3 - Article

VL - 21

SP - 1833

EP - 1840

JO - PCR Methods and Applications

JF - PCR Methods and Applications

SN - 1088-9051

IS - 11

ER -