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A unique chromatin signature uncovers early developmental enhancers in humans.
Rada-Iglesias A
,
Bajpai R
,
Swigut T
,
Brugmann SA
,
Flynn RA
,
Wysocka J
.
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Cell-fate transitions involve the integration of genomic information encoded by regulatory elements, such as enhancers, with the cellular environment. However, identification of genomic sequences that control human embryonic development represents a formidable challenge. Here we show that in human embryonic stem cells (hESCs), unique chromatin signatures identify two distinct classes of genomic elements, both of which are marked by the presence of chromatin regulators p300 and BRG1, monomethylation of histone H3 at lysine 4 (H3K4me1), and low nucleosomal density. In addition, elements of the first class are distinguished by the acetylation of histone H3 at lysine 27 (H3K27ac), overlap with previously characterized hESC enhancers, and are located proximally to genes expressed in hESCs and the epiblast. In contrast, elements of the second class, which we term 'poised enhancers', are distinguished by the absence of H3K27ac, enrichment of histone H3 lysine 27 trimethylation (H3K27me3), and are linked to genes inactive in hESCs and instead are involved in orchestrating early steps in embryogenesis, such as gastrulation, mesoderm formation and neurulation. Consistent with the poised identity, during differentiation of hESCs to neuroepithelium, a neuroectoderm-specific subset of poised enhancers acquires a chromatin signature associated with active enhancers. When assayed in zebrafish embryos, poised enhancers are able to direct cell-type and stage-specific expression characteristic of their proximal developmental gene, even in the absence of sequence conservation in the fish genome. Our data demonstrate that early developmental enhancers are epigenetically pre-marked in hESCs and indicate an unappreciated role of H3K27me3 at distal regulatory elements. Moreover, the wealth of new regulatory sequences identified here provides an invaluable resource for studies and isolation of transient, rare cell populations representing early stages of human embryogenesis.
Bajpai,
Molecular stages of rapid and uniform neuralization of human embryonic stem cells.
2009, Pubmed
Bajpai,
Molecular stages of rapid and uniform neuralization of human embryonic stem cells.
2009,
Pubmed
Blechinger,
The heat-inducible zebrafish hsp70 gene is expressed during normal lens development under non-stress conditions.
2002,
Pubmed
Boyer,
Core transcriptional regulatory circuitry in human embryonic stem cells.
2005,
Pubmed
Bulger,
Enhancers: the abundance and function of regulatory sequences beyond promoters.
2010,
Pubmed
Bulger,
Maps for changing landscapes: viewing epigenomic signatures through differentiation.
2012,
Pubmed
Cantone,
Unraveling epigenetic landscapes: the enigma of enhancers.
2011,
Pubmed
Chan,
KLF4 and PBX1 directly regulate NANOG expression in human embryonic stem cells.
2009,
Pubmed
Cockerill,
Human granulocyte-macrophage colony-stimulating factor enhancer function is associated with cooperative interactions between AP-1 and NFATp/c.
1995,
Pubmed
Danielian,
Engrailed-1 as a target of the Wnt-1 signalling pathway in vertebrate midbrain development.
1996,
Pubmed
Fisher,
Evaluating the biological relevance of putative enhancers using Tol2 transposon-mediated transgenesis in zebrafish.
2006,
Pubmed
Furlan-Magaril,
Sequential chromatin immunoprecipitation protocol: ChIP-reChIP.
2009,
Pubmed
Giresi,
Isolation of active regulatory elements from eukaryotic chromatin using FAIRE (Formaldehyde Assisted Isolation of Regulatory Elements).
2009,
Pubmed
Guenther,
A chromatin landmark and transcription initiation at most promoters in human cells.
2007,
Pubmed
Hallikas,
Genome-wide prediction of mammalian enhancers based on analysis of transcription-factor binding affinity.
2006,
Pubmed
Hancock,
Mapping and expression analysis of the mouse ortholog of Xenopus Eomesodermin.
1999,
Pubmed
,
Xenbase
Hargreaves,
Control of inducible gene expression by signal-dependent transcriptional elongation.
2009,
Pubmed
Harris,
Comparison of sequencing-based methods to profile DNA methylation and identification of monoallelic epigenetic modifications.
2010,
Pubmed
He,
Nucleosome dynamics define transcriptional enhancers.
2010,
Pubmed
Heintzman,
Distinct and predictive chromatin signatures of transcriptional promoters and enhancers in the human genome.
2007,
Pubmed
Heintzman,
Histone modifications at human enhancers reflect global cell-type-specific gene expression.
2009,
Pubmed
Ho,
An embryonic stem cell chromatin remodeling complex, esBAF, is an essential component of the core pluripotency transcriptional network.
2009,
Pubmed
Ieda,
Direct reprogramming of fibroblasts into functional cardiomyocytes by defined factors.
2010,
Pubmed
Itani,
Functional characterization of polymorphisms in the kidney enhancer of the human renin gene.
2007,
Pubmed
Kerppola,
Polycomb group complexes--many combinations, many functions.
2009,
Pubmed
Kim,
Widespread transcription at neuronal activity-regulated enhancers.
2010,
Pubmed
Marín,
Patterning of the basal telencephalon and hypothalamus is essential for guidance of cortical projections.
2002,
Pubmed
McLean,
GREAT improves functional interpretation of cis-regulatory regions.
2010,
Pubmed
Mito,
Histone replacement marks the boundaries of cis-regulatory domains.
2007,
Pubmed
Nakabayashi,
Functional mapping of tissue-specific elements of the human alpha-fetoprotein gene enhancer.
2004,
Pubmed
Navratilova,
Systematic human/zebrafish comparative identification of cis-regulatory activity around vertebrate developmental transcription factor genes.
2009,
Pubmed
Peng,
Jarid2/Jumonji coordinates control of PRC2 enzymatic activity and target gene occupancy in pluripotent cells.
2009,
Pubmed
,
Xenbase
Rahl,
c-Myc regulates transcriptional pause release.
2010,
Pubmed
Robb,
Cloning, expression analysis, and chromosomal localization of murine and human homologues of a Xenopus mix gene.
2000,
Pubmed
,
Xenbase
Ryan,
Eomesodermin, a key early gene in Xenopus mesoderm differentiation.
1996,
Pubmed
,
Xenbase
Segawa,
Identification of a novel distal enhancer in human adiponectin gene.
2009,
Pubmed
Sprague,
The Zebrafish Information Network: the zebrafish model organism database.
2006,
Pubmed
Valouev,
Genome-wide analysis of transcription factor binding sites based on ChIP-Seq data.
2008,
Pubmed
Visel,
Genomic views of distant-acting enhancers.
2009,
Pubmed
Visel,
ChIP-seq accurately predicts tissue-specific activity of enhancers.
2009,
Pubmed
Visel,
VISTA Enhancer Browser--a database of tissue-specific human enhancers.
2007,
Pubmed
Yeom,
Germline regulatory element of Oct-4 specific for the totipotent cycle of embryonal cells.
1996,
Pubmed
