Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

ChIP-seq Identification of Weakly Conserved Heart Enhancers

ABSTRACT: Accurate control of tissue-specific gene expression plays a pivotal role in heart development. However, few cardiac transcriptional enhancers have thus far been identified. Extreme non-coding sequence conservation successfully predicts enhancers active in many tissues, but fails to identify substantial numbers of enhancers active in the heart. We used ChIP-seq with the enhancer-associated protein p300 from mouse embryonic heart tissue to identify over three thousand candidate heart enhancers genome-wide. In contrast to other studied tissues at this time-point, most candidate heart enhancers are not deeply conserved in vertebrate evolution. Nevertheless, the testing of 130 candidate regions in a transgenic mouse assay revealed that most of them reproducibly function as enhancers active in the heart, irrespective of their degree of evolutionary constraint. These results provide evidence for tissue-dependent differences in evolutionary constraint of enhancers acting through the transcriptional co-activator p300 at this time-point, and identify a large population of poorly conserved heart enhancers. Examination of p300 binding in embryonic stage 11.5 mouse heart and midbrain

ORGANISM(S): Mus musculus

SUBMITTER: Matthew Blow

PROVIDER: E-GEOD-22549 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

ChIP-Seq identification of weakly conserved heart enhancers.

Blow Matthew J MJ McCulley David J DJ Li Zirong Z Zhang Tao T Akiyama Jennifer A JA Holt Amy A Plajzer-Frick Ingrid I Shoukry Malak M Wright Crystal C Chen Feng F Afzal Veena V Bristow James J Ren Bing B Black Brian L BL Rubin Edward M EM Visel Axel A Pennacchio Len A LA

Nature genetics 20100822 9

Accurate control of tissue-specific gene expression plays a pivotal role in heart development, but few cardiac transcriptional enhancers have thus far been identified. Extreme noncoding-sequence conservation has successfully predicted enhancers that are active in many tissues but has failed to identify substantial numbers of heart-specific enhancers. Here, we used ChIP-Seq with the enhancer-associated protein p300 from mouse embryonic day 11.5 heart tissue to identify over 3,000 candidate heart ...[more]

PMID: 20729851

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Project description:Identification of cell-type specific enhancers is important for understanding the regulation of programs controlling cellular development and differentiation. Enhancers are typically marked by the co-transcriptional activator protein p300 or by groups of cell-expressed transcription factors. We hypothesized that a unique set of enhancers regulates gene expression in human erythroid cells, a highly specialized cell type evolved to provide adequate amounts of oxygen throughout the body. Using chromatin immunoprecipitation followed by massively parallel sequencing, genome-wide maps of candidate enhancers were constructed for p300 and four transcription factors, GATA1, NF-E2, KLF1, and SCL, using primary human erythroid cells. These data were combined with gene expression analyses and candidate enhancers identified. Consistent with their predicted function as candidate enhancers, there was statistically significant enrichment of p300 and combinations of co-localizing erythroid transcription factors within 1-50 kb of the TSS of genes highly expressed in erythroid cells. Candidate enhancers were also enriched near genes with known erythroid cell function or erythroid cell phenotypes. Candidate enhancers exhibited only moderate conservation with mouse and minimal conservation with nonplacental vertebrates. Candidate enhancers were mapped to a data set of erythroid-associated, biologically relevant, SNPs from the GWAS catalog of the NHGRI. Fourteen candidate enhancers, representing 10 genetic loci, mapped to sites associated with biologically relevant erythroid traits. Fragments from these loci directed statistically significant expression in reporter gene assays. Identification of enhancers in human erythroid cells will allow a better understanding of erythroid cell development, differentiation, structure, and function, and provide insights into inherited and acquired hematologic disease. CD34+-selected stem and progenitor cells were expanded for three days in the absence of EPO. The cells were further cultured in the presence of EPO, and formaldehyde crosslinked chromatin was isolated after cells differentiated into R3/R4 nucleated erythroid cells. Chromatin Immunoprecipitation followed by sequencing (chIP-seq) was performed using antibodies against GATA1, KLF1, NFE2, TAL1, p300, H3K4me2 and H3K4me3, along with a total input control. Raw data (fastq, SRA) is missing for the TAL1 chIP-seq dataset

Dataset Information

ChIP-seq Identification of Weakly Conserved Heart Enhancers

Publications

ChIP-Seq identification of weakly conserved heart enhancers.

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