DNA methylation immediately adjacent to active histone marking does not silence transcription

Arie B. Brinkman; Sebastiaan W.C. Pennings; Georgia G. Braliou; Luc E.G. Rietveld; Hendrik G. Stunnenberg

doi:10.1093/nar/gkl1014

DNA methylation immediately adjacent to active histone marking does not silence transcription

Arie B. Brinkman, Sebastiaan W.C. Pennings, Georgia G. Braliou, Luc E.G. Rietveld, Hendrik G. Stunnenberg

Research output: Contribution to journal › Article › peer-review

21 Citations (Scopus)

Abstract

Active promoters generally contain histone H3/H4 hyperacetylation and tri-methylation at H3 lysine 4, whereas repressed promoters are associated with DNA methylation. Here we show that the repressed erythroid-specific carbonic anhydrase II (CAII) promoter has active histone modifications localized around the transcription start, while high levels of CpG methylation are present directly upstream from these active marks. Despite the presence of active histone modifications, the repressed promoter requires hormone-induced activation for efficient preinitiation complex assembly. Transient and positional changes in histone H3/H4 acetylation and local changes in nucleosome density are evident during activation, but the bipartite epigenetic code is stably maintained. Our results suggest that active histone modifications may prevent spreading of CpG methylation towards the promoter and show that repressive DNA methylation immediately adjacent to a promoter does not necessarily repress transcription.

Original language	English
Pages (from-to)	801-811
Number of pages	11
Journal	Nucleic acids research
Volume	35
Issue number	3
DOIs	https://doi.org/10.1093/nar/gkl1014
Publication status	Published - Feb 2007
Externally published	Yes

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@article{76fa68bac6a848ff8a4743cf784274a2,

title = "DNA methylation immediately adjacent to active histone marking does not silence transcription",

abstract = "Active promoters generally contain histone H3/H4 hyperacetylation and tri-methylation at H3 lysine 4, whereas repressed promoters are associated with DNA methylation. Here we show that the repressed erythroid-specific carbonic anhydrase II (CAII) promoter has active histone modifications localized around the transcription start, while high levels of CpG methylation are present directly upstream from these active marks. Despite the presence of active histone modifications, the repressed promoter requires hormone-induced activation for efficient preinitiation complex assembly. Transient and positional changes in histone H3/H4 acetylation and local changes in nucleosome density are evident during activation, but the bipartite epigenetic code is stably maintained. Our results suggest that active histone modifications may prevent spreading of CpG methylation towards the promoter and show that repressive DNA methylation immediately adjacent to a promoter does not necessarily repress transcription.",

author = "Brinkman, \{Arie B.\} and Pennings, \{Sebastiaan W.C.\} and Braliou, \{Georgia G.\} and Rietveld, \{Luc E.G.\} and Stunnenberg, \{Hendrik G.\}",

note = "Funding Information: We thank Olivier Gandrillon and Sandrine Giraud for providing T2EC cells and related technical advice, Thomas Jenuwein for providing the H3K9(tri-)methyl antiserum, Rolf Ohlsson and members of the Stunnenberg lab for helpful discussions. This research was supported by Dutch Cancer Foundation (KWF) grants KUN 2003-2932 to A.B.B. and KUN 98-1802 to L.E.G.R. Funding to pay the Open Access publication charges for this article was provided by Dutch Cancer Foundation (KWF) grants KUN 2003-2932.",

year = "2007",

month = feb,

doi = "10.1093/nar/gkl1014",

language = "English",

volume = "35",

pages = "801--811",

journal = "Nucleic acids research",

issn = "0305-1048",

publisher = "Oxford University Press",

number = "3",

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TY - JOUR

T1 - DNA methylation immediately adjacent to active histone marking does not silence transcription

AU - Brinkman, Arie B.

AU - Pennings, Sebastiaan W.C.

AU - Braliou, Georgia G.

AU - Rietveld, Luc E.G.

AU - Stunnenberg, Hendrik G.

N1 - Funding Information: We thank Olivier Gandrillon and Sandrine Giraud for providing T2EC cells and related technical advice, Thomas Jenuwein for providing the H3K9(tri-)methyl antiserum, Rolf Ohlsson and members of the Stunnenberg lab for helpful discussions. This research was supported by Dutch Cancer Foundation (KWF) grants KUN 2003-2932 to A.B.B. and KUN 98-1802 to L.E.G.R. Funding to pay the Open Access publication charges for this article was provided by Dutch Cancer Foundation (KWF) grants KUN 2003-2932.

PY - 2007/2

Y1 - 2007/2

N2 - Active promoters generally contain histone H3/H4 hyperacetylation and tri-methylation at H3 lysine 4, whereas repressed promoters are associated with DNA methylation. Here we show that the repressed erythroid-specific carbonic anhydrase II (CAII) promoter has active histone modifications localized around the transcription start, while high levels of CpG methylation are present directly upstream from these active marks. Despite the presence of active histone modifications, the repressed promoter requires hormone-induced activation for efficient preinitiation complex assembly. Transient and positional changes in histone H3/H4 acetylation and local changes in nucleosome density are evident during activation, but the bipartite epigenetic code is stably maintained. Our results suggest that active histone modifications may prevent spreading of CpG methylation towards the promoter and show that repressive DNA methylation immediately adjacent to a promoter does not necessarily repress transcription.

AB - Active promoters generally contain histone H3/H4 hyperacetylation and tri-methylation at H3 lysine 4, whereas repressed promoters are associated with DNA methylation. Here we show that the repressed erythroid-specific carbonic anhydrase II (CAII) promoter has active histone modifications localized around the transcription start, while high levels of CpG methylation are present directly upstream from these active marks. Despite the presence of active histone modifications, the repressed promoter requires hormone-induced activation for efficient preinitiation complex assembly. Transient and positional changes in histone H3/H4 acetylation and local changes in nucleosome density are evident during activation, but the bipartite epigenetic code is stably maintained. Our results suggest that active histone modifications may prevent spreading of CpG methylation towards the promoter and show that repressive DNA methylation immediately adjacent to a promoter does not necessarily repress transcription.

UR - https://www.scopus.com/pages/publications/33847389340

U2 - 10.1093/nar/gkl1014

DO - 10.1093/nar/gkl1014

M3 - Article

C2 - 17202157

AN - SCOPUS:33847389340

SN - 0305-1048

VL - 35

SP - 801

EP - 811

JO - Nucleic acids research

JF - Nucleic acids research

IS - 3

ER -

DNA methylation immediately adjacent to active histone marking does not silence transcription

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