Faculty Collaboration Database

RNA polymerase II binding patterns reveal genomic regions involved in microRNA gene regulation. PLoS One 2010 Nov 02;5(11):e13798

Date

11/13/2010

Pubmed ID

21072189

Pubmed Central ID

PMC2970572

DOI

10.1371/journal.pone.0013798

Scopus ID

2-s2.0-78249233850 (requires institutional sign-in at Scopus site)   49 Citations

Abstract

MicroRNAs are small non-coding RNAs involved in post-transcriptional regulation of gene expression. Due to the poor annotation of primary microRNA (pri-microRNA) transcripts, the precise location of promoter regions driving expression of many microRNA genes is enigmatic. This deficiency hinders our understanding of microRNA-mediated regulatory networks. In this study, we develop a computational approach to identify the promoter region and transcription start site (TSS) of pri-microRNAs actively transcribed using genome-wide RNA Polymerase II (RPol II) binding patterns derived from ChIP-seq data. Based upon the assumption that the distribution of RPol II binding patterns around the TSS of microRNA and protein coding genes are similar, we designed a statistical model to mimic RPol II binding patterns around the TSS of highly expressed, well-annotated promoter regions of protein coding genes. We used this model to systematically scan the regions upstream of all intergenic microRNAs for RPol II binding patterns similar to those of TSS from protein coding genes. We validated our findings by examining the conservation, CpG content, and activating histone marks in the identified promoter regions. We applied our model to assess changes in microRNA transcription in steroid hormone-treated breast cancer cells. The results demonstrate many microRNA genes have lost hormone-dependent regulation in tamoxifen-resistant breast cancer cells. MicroRNA promoter identification based upon RPol II binding patterns provides important temporal and spatial measurements regarding the initiation of transcription, and therefore allows comparison of transcription activities between different conditions, such as normal and disease states.

Author List

Wang G, Wang Y, Shen C, Huang YW, Huang K, Huang TH, Nephew KP, Li L, Liu Y

MESH terms used to index this publication - Major topics in bold

Algorithms
Cell Line, Tumor
Chromatin Immunoprecipitation
Computational Biology
CpG Islands
Gene Expression Regulation
Histones
Humans
Lysine
Methylation
MicroRNAs
Promoter Regions, Genetic
Protein Binding
RNA Polymerase II
Regulatory Sequences, Nucleic Acid
Transcription Initiation Site
Transcription, Genetic