title: Extreme HOT regions are CpG-dense promoters in C. elegans and humans.
abstract: Most vertebrate promoters lie in unmethylated CpG-dense islands, whereas methylation of the more sparsely distributed CpGs in the remainder of the genome is thought to contribute to transcriptional repression. Nonmethylated CG dinucleotides are recognized by CXXC finger protein 1 (CXXC1, also known as CFP1), which recruits SETD1A (also known as Set1) methyltransferase for trimethylation of histone H3 lysine 4, an active promoter mark. Genomic regions enriched for CpGs are thought to be either absent or irrelevant in invertebrates that lack DNA methylation, such as C. elegans; however, a CXXC1 ortholog (CFP-1) is present. Here we demonstrate that C. elegans CFP-1 targets promoters with high CpG density, and these promoters are marked by high levels of H3K4me3. Furthermore, as for mammalian promoters, high CpG content is associated with nucleosome depletion irrespective of transcriptional activity. We further show that highly occupied target (HOT) regions identified by the binding of a large number of transcription factors are CpG-rich promoters in C. elegans and human genomes, suggesting that the unusually high factor association at HOT regions may be a consequence of CpG-linked chromatin accessibility. Our results indicate that nonmethylated CpG-dense sequence is a conserved genomic signal that promotes an open chromatin state, targeting by a CXXC1 ortholog, and H3K4me3 modification in both C. elegans and human genomes.
authors.affiliation: The Gurdon Institute and Department of Genetics, University of Cambridge, Cambridge CB3 0DH, United Kingdom.
authors.forename: Ron A-J
authors.initials: RA
authors.lastname: Chen
authors.affiliation: The Gurdon Institute and Department of Genetics, University of Cambridge, Cambridge CB3 0DH, United Kingdom.
authors.forename: Przemyslaw
authors.initials: P
authors.lastname: Stempor
authors.affiliation: The Gurdon Institute and Department of Genetics, University of Cambridge, Cambridge CB3 0DH, United Kingdom.
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Down
authors.affiliation: The Gurdon Institute and Department of Genetics, University of Cambridge, Cambridge CB3 0DH, United Kingdom.
authors.forename: Eva
authors.initials: E
authors.lastname: Zeiser
authors.affiliation: The Gurdon Institute and Department of Genetics, University of Cambridge, Cambridge CB3 0DH, United Kingdom.
authors.forename: Sky K
authors.initials: SK
authors.lastname: Feuer
authors.affiliation: The Gurdon Institute and Department of Genetics, University of Cambridge, Cambridge CB3 0DH, United Kingdom.
authors.forename: Julie
authors.initials: J
authors.lastname: Ahringer
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000378:metabolism; D018899:CpG Islands; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D057890:Epigenomics; D015870:Gene Expression; D005786:Gene Expression Regulation; D023061:Gene Order; D017930:Genes, Reporter; D005822:Genetic Vectors / Q000235:genetics; D006657:Histones / Q000378:metabolism; D006801:Humans; D009707:Nucleosomes / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D006657:Histones; D009707:Nucleosomes; D014157:Transcription Factors