DNA methylation immediately adjacent to active histone marking does not silence transcription.
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.
Brinkman
Arie B
AB
Department of Molecular Biology, Nijmegen Centre for Molecular Life Sciences, Radboud University, The Netherlands.
Pennings
Sebastiaan W C
SW
Braliou
Georgia G
GG
Rietveld
Luc E G
LE
Stunnenberg
Hendrik G
HG
D000107:Acetylation; D000818:Animals; D024402:Carbonic Anhydrase II / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D018899:CpG Islands; D019175:DNA Methylation; D015672:Erythroid Precursor Cells / Q000378:metabolism; D020868:Gene Silencing; D006657:Histones / Q000737:chemistry / Q000378:metabolism*; D009707:Nucleosomes / Q000378:metabolism; D011401:Promoter Regions, Genetic; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D014284:Triiodothyronine / Q000494:pharmacology
D006657:Histones; D009707:Nucleosomes; D014157:Transcription Factors; D014284:Triiodothyronine; D024402:Carbonic Anhydrase II