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      Genomic occupancy of the transcriptional co-activators p300 and CBP

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      Author(s): , *
      Publication date (Electronic):
      Journal: Transcription
      Publisher: Landes Bioscience
      Keywords: transcription, p300, CBP, ChIP-seq, enhancer, Polycomb

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          Abstract

          The p300 and CBP co-activators are histone acetylases and central regulators of transcription in metazoans. The genomic occupancy of p300/CBP detected by ChIP-seq experiments can be used to identify transcriptional enhancers. However, studies in Drosophila embryos suggest that there is a preference for some transcription factors in directing p300/CBP to the genome. Although p300/CBP occupancy in general correlates with gene activation, they can also be found at silent genomic regions, which does not result in histone acetylation. Polycomb-mediated H3K27me3 is associated with repression, but does not preclude p300/CBP binding. An antagonism between H3K27ac and H3K27me3 indicates that p300/CBP may be involved in switching between repressed and active chromatin states.

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          A unique chromatin signature uncovers early developmental enhancers in humans.

          Alvaro Rada-Iglesias, Ruchi Bajpai, Tomek Swigut … (2011)
          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.
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            ChIP-seq accurately predicts tissue-specific activity of enhancers.

            Axel Visel, Matthew J. Blow, Zirong Li … (2009)
            A major yet unresolved quest in decoding the human genome is the identification of the regulatory sequences that control the spatial and temporal expression of genes. Distant-acting transcriptional enhancers are particularly challenging to uncover because they are scattered among the vast non-coding portion of the genome. Evolutionary sequence constraint can facilitate the discovery of enhancers, but fails to predict when and where they are active in vivo. Here we present the results of chromatin immunoprecipitation with the enhancer-associated protein p300 followed by massively parallel sequencing, and map several thousand in vivo binding sites of p300 in mouse embryonic forebrain, midbrain and limb tissue. We tested 86 of these sequences in a transgenic mouse assay, which in nearly all cases demonstrated reproducible enhancer activity in the tissues that were predicted by p300 binding. Our results indicate that in vivo mapping of p300 binding is a highly accurate means for identifying enhancers and their associated activities, and suggest that such data sets will be useful to study the role of tissue-specific enhancers in human biology and disease on a genome-wide scale.
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              Identification of functional elements and regulatory circuits by Drosophila modENCODE.

              Sushmita Roy, Jason Ernst, Peter V. Kharchenko … (2011)
              To gain insight into how genomic information is translated into cellular and developmental programs, the Drosophila model organism Encyclopedia of DNA Elements (modENCODE) project is comprehensively mapping transcripts, histone modifications, chromosomal proteins, transcription factors, replication proteins and intermediates, and nucleosome properties across a developmental time course and in multiple cell lines. We have generated more than 700 data sets and discovered protein-coding, noncoding, RNA regulatory, replication, and chromatin elements, more than tripling the annotated portion of the Drosophila genome. Correlated activity patterns of these elements reveal a functional regulatory network, which predicts putative new functions for genes, reveals stage- and tissue-specific regulators, and enables gene-expression prediction. Our results provide a foundation for directed experimental and computational studies in Drosophila and related species and also a model for systematic data integration toward comprehensive genomic and functional annotation.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Transcription
                Journal ID (iso-abbrev): Transcription
                Journal ID (publisher-id): TRSC
                Title: Transcription
                Publisher: Landes Bioscience
                ISSN (Print): 2154-1264
                ISSN (Electronic): 2154-1272
                Publication date (Print): 01 January 2013
                Publication date (Electronic): 06 November 2012
                Publication date PMC-release: 06 November 2012
                Volume: 4
                Issue: 1
                Pages: 18-23
                Affiliations
                The Wenner-Gren Institute; Developmental Biology; Stockholm University; Arrheniuslaboratories E3, SE-106 91 Stockholm, Sweden
                Author notes
                [* ]Correspondence to: Mattias Mannervik, Email: mannervik@ 123456devbio.su.se
                Article
                Publisher ID: 2012TRANS0050R Publisher Item ID: 22601
                DOI: 10.4161/trns.22601
                PMC ID: 3644037
                PubMed ID: 23131664
                SO-VID: 625a46b5-e416-4b00-9a4b-e79dd03ab755
                Copyright © Copyright © 2013 Landes Bioscience
                License:

                This is an open-access article licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License. The article may be redistributed, reproduced, and reused for non-commercial purposes, provided the original source is properly cited.

                History
                Date received : 02 October 2012
                Date revision received : 18 October 2012
                Date accepted : 19 October 2012
                Categories
                Subject: Point of View

                ScienceOpen disciplines: Molecular biology
                Keywords: transcription,p300,cbp,chip-seq,enhancer,polycomb
                Data availability:
                ScienceOpen disciplines: Molecular biology
                Keywords: transcription, p300, cbp, chip-seq, enhancer, polycomb

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