About this study
Gene transcription in animals involves the assembly of RNA polymerase II at core promoters and its cell-type-specific activation by enhancers that can be located more distally. However, how ubiquitous expression of housekeeping genes is achieved has been less clear. In particular, it is unknown whether ubiquitously active enhancers exist and how developmental and housekeeping gene regulation is separated. An attractive hypothesis is that different core promoters might exhibit an intrinsic specificity to certain enhancers. This is conceivable, as various core promoter sequence elements are differentially distributed between genes of different functions, including elements that are predominantly found at either developmentally regulated or at housekeeping genes. Here we show that thousands of enhancers in Drosophila melanogaster S2 and ovarian somatic cells (OSCs) exhibit a marked specificity to one of two core promoters—one derived from a ubiquitously expressed ribosomal protein gene and another from a developmentally regulated transcription factor—and confirm the existence of these two classes for five additional core promoters from genes with diverse functions. Housekeeping enhancers are active across the two cell types, while developmental enhancers exhibit strong cell-type specificity. Both enhancer classes differ in their genomic distribution, the functions of neighbouring genes, and the core promoter elements of these neighbouring genes. In addition, we identify two transcription factors—Dref and Trl—that bind and activate housekeeping versus developmental enhancers, respectively. Our results provide evidence for a sequence-encoded enhancer–core-promoter specificity that separates developmental and housekeeping gene regulatory programs for thousands of enhancers and their target genes across the entire genome.
Full author list & citation
Muhammad A. Zabidi, Cosmas D. Arnold, Katharina Schernhuber, Michaela Pagani, Martina Rath, Olga Frank, Alexander Stark. Enhancer–core-promoter specificity separates developmental and housekeeping gene regulation. 2014-12-15. https://doi.org/10.1038/nature13994
Experiments 3
E1OX8L0K7
Approximately 500-bp sheared Drosophila melanogaster genomic fragments were cloned into self-transcribing STARR-seq reporters carrying RpS12, DSCP, eEF1delta, x16, NipB, or pnr core promoters and screened in S2 cells. The table contains author-called peak summits and input-normalized activities from the six deposited genome-wide promoter contexts; RpS12 and DSCP are merged two-replicate screens, while several additional contexts have only one deposited peak file.
E6KK5LI21
Whole-genome sheared Drosophila melanogaster fragments were screened in ovarian somatic cells (OSCs) with STARR-seq reporters carrying the RpS12 housekeeping core promoter or the DSCP developmental core promoter. The table contains author-merged two-replicate peak calls for both promoter contexts and the derived 501-bp specificity class.
E9R802YWG
A focused STARR-seq library made from 29 BACs covering approximately 5 Mb of Drosophila melanogaster genomic sequence was screened in S2 cells with nine core-promoter reporters: RpS12, DSCP, eEF1delta, x16, NipB, pnr, Hsp70, eve, and eve-long. The table contains the author-called peak summits and input-normalized activities, annotated to the BAC interval from Supplementary Table 16.