Dataset Information

Genome-wide quantitative enhancer activity maps identified by STARR-seq

ABSTRACT: Genomic enhancers are important regulators of gene expression, but their identification is a challenge and methods depend on indirect measures of activity. We developed a method termed STARR-seq to directly and quantitatively assess enhancer activity for millions of candidates from arbitrary sources of DNA, enabling screens across entire genomes. When applied to the Drosophila genome, STARR-seq identifies thousands of cell type-specific enhancers across a broad continuum of strengths, linking differential gene expression to differences in enhancer activity and creating a genome-wide quantitative enhancer map. This map reveals the highly complex regulation of transcription, with several independent enhancers for both developmental regulators and ubiquitously expressed genes. STARR-seq can be used to identify and quantitate enhancer activity in other eukaryotes, including human.

ORGANISM(S): Homo sapiens Drosophila melanogaster

PROVIDER: GSE40739 | GEO | 2013/01/17

SECONDARY ACCESSION(S): PRJNA175267

REPOSITORIES: GEO

ACCESS DATA

Similar Datasets

Project description:Development and homeostasis of all multicellular organisms rely on differential cell-type-specific gene expression that is regulated by non-coding genomic enhancer elements. Enhancers function through the transcription-factor-mediated recruitment of cofactors, a structurally and functionally diverse set of proteins that activate RNA polymerase II transcription at promoters. Despite the important roles of enhancers and cofactors in transcriptional regulation, it is still not clear if all cofactors are required for all enhancers or if different enhancers have distinct cofactor dependencies and whether differential cofactor dependencies could be used to functionally categorize enhancers. Here, we quantified enhancer activities along the entire human genome using the massively parallel enhancer-activity assay STARR-seq in HCT116 cells, following the rapid auxin-inducible degradation of eight different cofactors. We identified groups of enhancers with distinct cofactor requirements, including enhancers whose activity is insensitive to the depletion of the core Mediator subunit MED14 or the bromodomain protein BRD4, respectively. In particular, Mediator seemed dispensable for P53-responsive enhancers and MED14-depleted cells in which transcription globally failed were still able to induce endogenous P53 target genes such as p21. Similarly, BRD4 was not required for genes with a CCAAT- and TATA-box proximal enhancer, including histone genes and LTR12 family retrotransposons, and for the induction of TATA-box containing heat-shock genes. Taken together, we show that different types of enhancers with distinct cofactor dependencies exist, including enhancer types that function in the absence of well-known cofactors and are employed to regulate specific gene classes and transcriptional programs. This represents the first functional categorization of enhancers by their cofactor dependencies that improves our understanding of alternative ways to activate transcription, which can aid in developing more precise interventions to modulate gene expression. "

Dataset Information

Genome-wide quantitative enhancer activity maps identified by STARR-seq

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure