High-resolution human core-promoter prediction with CoreBoost_HM

Abstract

Correctly locating the gene transcription start site and the core-promoter is important for understanding transcriptional regulation mechanism. Here we have integrated specific genome-wide histone modification and DNA sequence features together to predict RNA polymerase II core-promoters in the human genome. Our new predictor CoreBoost_HM outperforms existing promoter prediction algorithms by providing significantly higher sensitivity and specificity at high resolution. We demonstrated that even though the histone modification data used in this study are from a specific cell type (CD4+ T-cell), our method can be used to identify both active and repressed promoters. We have applied it to search the upstream regions of microRNA genes, and show that CoreBoost_HM can accurately identify the known promoters of the intergenic microRNAs. We also identified a few intronic microRNAs that may have their own promoters. This result suggests that our new method can help to identify and characterize the core-promoters of both coding and noncoding genes.

MiR-125 in normal and malignant hematopoiesis

“…[6][7][8][9] This hypothesis is supported by recent research predicting miRNA promoters by combining bioinformatic analysis of nearby upstream DNA regulatory elements (transcription start sites (TSS), conserved transcription factor-binding sites, TATA boxes, A/B boxes) and epigenetic modifications (CpG islands, histone modifications, nucleosome positioning patterns) with chromatin immunopreciptiation screens or reporter assays. [6][7][8][9][10][11] It seems that about half of the miRNAs located in introns of protein-coding genes (B60%) contain putative promoters regulating transcription independent of their host gene. 7 This is also supported by the observed discrepancy in expression of several miRNAs and their host genes.…”

“…Several independent putative promoters have been described (Figure 1b). One that drives co-expression of hsa-miR-100 and hsa-let-7a-2 independent of their potential host gene, [6][7][8][9] one that drives co-expression of hsa-miR-99a and hsa-let-7c independent of their host gene, [6][7][8][9]11 and another that drives co-expression of hsa-miR-99b, hsa-let-7c and hsa-miR-125a.…”

“…Hsa-let-7a-2 Hsa-miR-125b-1 A putative promoter predicted by Long et al, 7 Wang et al, 9 Ozsolak et al 8 and Corcoran et al 6 2: A putative promoter predicted by Long et al, 7 Wang et al, 9 and Corcoran et al 6 3: A putative promoter predicted by Long et al, 7 Wang et al, 9 Ozsolak et al, 8 Corcoran et al, 6 and Montey et al…”

Illuminating microRNA Transcription from the Epigenome

“…Three of the most recent efforts, from Saini et al [22]; Wang et al [23]; and Wang et al [24], involved comprehensive genome-wide scans for known and predicted features of transcription start [22-24] and end regions [22]. These in silico analyses offered new predictive insights into miRNA promoters and pri-miRNA structure, which provided further impetus for large-scale experimental validation in diverse cell types.…”

Identifying regulatory elements in eukaryotic genomes

“…These concentrations of TFs and their PWMs have been used to model the likelihood of a DNA sequence driving expression of a segmentation gene and hence being a regulatory element [171,172]. Some methods have shown significant improvements in the accuracy of detecting CRMs using chromatin information, either in the form of histone modification data [173,174] or DNase HS data [175].…”