DNA hypomethylation within specific transposable element families associates with tissue-specific enhancer landscape

Mingchao Xie, Chibo Hong, Bo Zhang, Rebecca F. Lowdon, Xiaoyun Xing, Daofeng Li, Xin Zhou, Hyung Joo Lee, Cecile L. Maire, Keith L. Ligon, Philippe Gascard, Mahvash Sigaroudinia, Thea D. Tlsty, Theresa Kadlecek, Arthur Weiss, Henriette O'Geen, Peggy J. Farnham, Pamela A F Madden, Andrew J. Mungall, Angela Tam & 7 others Baljit Kamoh, Stephanie Cho, Richard Moore, Martin Hirst, Marco A. Marra, Joseph F. Costello, Ting Wang

Research output: Contribution to journalArticle

106 Citations (Scopus)

Abstract

Transposable element (TE)-derived sequences comprise half of the human genome and DNA methylome and are presumed to be densely methylated and inactive. Examination of genome-wide DNA methylation status within 928 TE subfamilies in human embryonic and adult tissues identified unexpected tissue-specific and subfamily-specific hypomethylation signatures. Genes proximal to tissue-specific hypomethylated TE sequences were enriched for functions important for the relevant tissue type, and their expression correlated strongly with hypomethylation within the TEs. When hypomethylated, these TE sequences gained tissue-specific enhancer marks, including monomethylation of histone H3 at lysine 4 (H3K4me1) and occupancy by p300, and a majority exhibited enhancer activity in reporter gene assays. Many such TEs also harbored binding sites for transcription factors that are important for tissue-specific functions and showed evidence of evolutionary selection. These data suggest that sequences derived from TEs may be responsible for wiring tissue type-specific regulatory networks and may have acquired tissue-specific epigenetic regulation.

Original languageEnglish (US)
Pages (from-to)836-841
Number of pages6
JournalNature Genetics
Volume45
Issue number7
DOIs
StatePublished - Jul 2013
Externally publishedYes

Fingerprint

DNA Transposable Elements
DNA
Human Genome
DNA Methylation
Reporter Genes
Epigenomics
Histones
Lysine
Transcription Factors
Binding Sites
Genome

ASJC Scopus subject areas

  • Genetics

Cite this

DNA hypomethylation within specific transposable element families associates with tissue-specific enhancer landscape. / Xie, Mingchao; Hong, Chibo; Zhang, Bo; Lowdon, Rebecca F.; Xing, Xiaoyun; Li, Daofeng; Zhou, Xin; Lee, Hyung Joo; Maire, Cecile L.; Ligon, Keith L.; Gascard, Philippe; Sigaroudinia, Mahvash; Tlsty, Thea D.; Kadlecek, Theresa; Weiss, Arthur; O'Geen, Henriette; Farnham, Peggy J.; Madden, Pamela A F; Mungall, Andrew J.; Tam, Angela; Kamoh, Baljit; Cho, Stephanie; Moore, Richard; Hirst, Martin; Marra, Marco A.; Costello, Joseph F.; Wang, Ting.

In: Nature Genetics, Vol. 45, No. 7, 07.2013, p. 836-841.

Research output: Contribution to journalArticle

Xie, M, Hong, C, Zhang, B, Lowdon, RF, Xing, X, Li, D, Zhou, X, Lee, HJ, Maire, CL, Ligon, KL, Gascard, P, Sigaroudinia, M, Tlsty, TD, Kadlecek, T, Weiss, A, O'Geen, H, Farnham, PJ, Madden, PAF, Mungall, AJ, Tam, A, Kamoh, B, Cho, S, Moore, R, Hirst, M, Marra, MA, Costello, JF & Wang, T 2013, 'DNA hypomethylation within specific transposable element families associates with tissue-specific enhancer landscape', Nature Genetics, vol. 45, no. 7, pp. 836-841. https://doi.org/10.1038/ng.2649
Xie, Mingchao ; Hong, Chibo ; Zhang, Bo ; Lowdon, Rebecca F. ; Xing, Xiaoyun ; Li, Daofeng ; Zhou, Xin ; Lee, Hyung Joo ; Maire, Cecile L. ; Ligon, Keith L. ; Gascard, Philippe ; Sigaroudinia, Mahvash ; Tlsty, Thea D. ; Kadlecek, Theresa ; Weiss, Arthur ; O'Geen, Henriette ; Farnham, Peggy J. ; Madden, Pamela A F ; Mungall, Andrew J. ; Tam, Angela ; Kamoh, Baljit ; Cho, Stephanie ; Moore, Richard ; Hirst, Martin ; Marra, Marco A. ; Costello, Joseph F. ; Wang, Ting. / DNA hypomethylation within specific transposable element families associates with tissue-specific enhancer landscape. In: Nature Genetics. 2013 ; Vol. 45, No. 7. pp. 836-841.
@article{c0366aa194034addaf706ed0fccda8f1,
title = "DNA hypomethylation within specific transposable element families associates with tissue-specific enhancer landscape",
abstract = "Transposable element (TE)-derived sequences comprise half of the human genome and DNA methylome and are presumed to be densely methylated and inactive. Examination of genome-wide DNA methylation status within 928 TE subfamilies in human embryonic and adult tissues identified unexpected tissue-specific and subfamily-specific hypomethylation signatures. Genes proximal to tissue-specific hypomethylated TE sequences were enriched for functions important for the relevant tissue type, and their expression correlated strongly with hypomethylation within the TEs. When hypomethylated, these TE sequences gained tissue-specific enhancer marks, including monomethylation of histone H3 at lysine 4 (H3K4me1) and occupancy by p300, and a majority exhibited enhancer activity in reporter gene assays. Many such TEs also harbored binding sites for transcription factors that are important for tissue-specific functions and showed evidence of evolutionary selection. These data suggest that sequences derived from TEs may be responsible for wiring tissue type-specific regulatory networks and may have acquired tissue-specific epigenetic regulation.",
author = "Mingchao Xie and Chibo Hong and Bo Zhang and Lowdon, {Rebecca F.} and Xiaoyun Xing and Daofeng Li and Xin Zhou and Lee, {Hyung Joo} and Maire, {Cecile L.} and Ligon, {Keith L.} and Philippe Gascard and Mahvash Sigaroudinia and Tlsty, {Thea D.} and Theresa Kadlecek and Arthur Weiss and Henriette O'Geen and Farnham, {Peggy J.} and Madden, {Pamela A F} and Mungall, {Andrew J.} and Angela Tam and Baljit Kamoh and Stephanie Cho and Richard Moore and Martin Hirst and Marra, {Marco A.} and Costello, {Joseph F.} and Ting Wang",
year = "2013",
month = "7",
doi = "10.1038/ng.2649",
language = "English (US)",
volume = "45",
pages = "836--841",
journal = "Nature Genetics",
issn = "1061-4036",
publisher = "Nature Publishing Group",
number = "7",

}

TY - JOUR

T1 - DNA hypomethylation within specific transposable element families associates with tissue-specific enhancer landscape

AU - Xie, Mingchao

AU - Hong, Chibo

AU - Zhang, Bo

AU - Lowdon, Rebecca F.

AU - Xing, Xiaoyun

AU - Li, Daofeng

AU - Zhou, Xin

AU - Lee, Hyung Joo

AU - Maire, Cecile L.

AU - Ligon, Keith L.

AU - Gascard, Philippe

AU - Sigaroudinia, Mahvash

AU - Tlsty, Thea D.

AU - Kadlecek, Theresa

AU - Weiss, Arthur

AU - O'Geen, Henriette

AU - Farnham, Peggy J.

AU - Madden, Pamela A F

AU - Mungall, Andrew J.

AU - Tam, Angela

AU - Kamoh, Baljit

AU - Cho, Stephanie

AU - Moore, Richard

AU - Hirst, Martin

AU - Marra, Marco A.

AU - Costello, Joseph F.

AU - Wang, Ting

PY - 2013/7

Y1 - 2013/7

N2 - Transposable element (TE)-derived sequences comprise half of the human genome and DNA methylome and are presumed to be densely methylated and inactive. Examination of genome-wide DNA methylation status within 928 TE subfamilies in human embryonic and adult tissues identified unexpected tissue-specific and subfamily-specific hypomethylation signatures. Genes proximal to tissue-specific hypomethylated TE sequences were enriched for functions important for the relevant tissue type, and their expression correlated strongly with hypomethylation within the TEs. When hypomethylated, these TE sequences gained tissue-specific enhancer marks, including monomethylation of histone H3 at lysine 4 (H3K4me1) and occupancy by p300, and a majority exhibited enhancer activity in reporter gene assays. Many such TEs also harbored binding sites for transcription factors that are important for tissue-specific functions and showed evidence of evolutionary selection. These data suggest that sequences derived from TEs may be responsible for wiring tissue type-specific regulatory networks and may have acquired tissue-specific epigenetic regulation.

AB - Transposable element (TE)-derived sequences comprise half of the human genome and DNA methylome and are presumed to be densely methylated and inactive. Examination of genome-wide DNA methylation status within 928 TE subfamilies in human embryonic and adult tissues identified unexpected tissue-specific and subfamily-specific hypomethylation signatures. Genes proximal to tissue-specific hypomethylated TE sequences were enriched for functions important for the relevant tissue type, and their expression correlated strongly with hypomethylation within the TEs. When hypomethylated, these TE sequences gained tissue-specific enhancer marks, including monomethylation of histone H3 at lysine 4 (H3K4me1) and occupancy by p300, and a majority exhibited enhancer activity in reporter gene assays. Many such TEs also harbored binding sites for transcription factors that are important for tissue-specific functions and showed evidence of evolutionary selection. These data suggest that sequences derived from TEs may be responsible for wiring tissue type-specific regulatory networks and may have acquired tissue-specific epigenetic regulation.

UR - http://www.scopus.com/inward/record.url?scp=84879611157&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84879611157&partnerID=8YFLogxK

U2 - 10.1038/ng.2649

DO - 10.1038/ng.2649

M3 - Article

VL - 45

SP - 836

EP - 841

JO - Nature Genetics

JF - Nature Genetics

SN - 1061-4036

IS - 7

ER -