RNA Polymerase II Binding Patterns Reveal Genomic Regions Involved in MicroRNA Gene Regulation

Guohua Wang, Yadong Wang, Changyu Shen, Yi wen Huang, Kun Huang, Tim H M Huang, Kenneth Nephew, Lang Li, Yunlong Liu

Research output: Contribution to journalArticle

42 Citations (Scopus)

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 primicroRNAs 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.

Original languageEnglish
Article numbere13798
JournalPLoS One
Volume5
Issue number11
DOIs
StatePublished - 2010

Fingerprint

RNA Polymerase II
DNA-directed RNA polymerase
MicroRNAs
microRNA
Gene expression
genomics
transcription (genetics)
Genes
Transcription Initiation Site
Genetic Promoter Regions
promoter regions
genes
Transcription
breast neoplasms
Histone Code
Steroid hormones
Cells
Hormones
Breast Neoplasms
tamoxifen

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

RNA Polymerase II Binding Patterns Reveal Genomic Regions Involved in MicroRNA Gene Regulation. / Wang, Guohua; Wang, Yadong; Shen, Changyu; Huang, Yi wen; Huang, Kun; Huang, Tim H M; Nephew, Kenneth; Li, Lang; Liu, Yunlong.

In: PLoS One, Vol. 5, No. 11, e13798, 2010.

Research output: Contribution to journalArticle

Wang, Guohua ; Wang, Yadong ; Shen, Changyu ; Huang, Yi wen ; Huang, Kun ; Huang, Tim H M ; Nephew, Kenneth ; Li, Lang ; Liu, Yunlong. / RNA Polymerase II Binding Patterns Reveal Genomic Regions Involved in MicroRNA Gene Regulation. In: PLoS One. 2010 ; Vol. 5, No. 11.
@article{939ec93a0bf5477ca1c3365931ced775,
title = "RNA Polymerase II Binding Patterns Reveal Genomic Regions Involved in MicroRNA Gene Regulation",
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 primicroRNAs 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 = "Guohua Wang and Yadong Wang and Changyu Shen and Huang, {Yi wen} and Kun Huang and Huang, {Tim H M} and Kenneth Nephew and Lang Li and Yunlong Liu",
year = "2010",
doi = "10.1371/journal.pone.0013798",
language = "English",
volume = "5",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "11",

}

TY - JOUR

T1 - RNA Polymerase II Binding Patterns Reveal Genomic Regions Involved in MicroRNA Gene Regulation

AU - Wang, Guohua

AU - Wang, Yadong

AU - Shen, Changyu

AU - Huang, Yi wen

AU - Huang, Kun

AU - Huang, Tim H M

AU - Nephew, Kenneth

AU - Li, Lang

AU - Liu, Yunlong

PY - 2010

Y1 - 2010

N2 - 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 primicroRNAs 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.

AB - 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 primicroRNAs 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.

UR - http://www.scopus.com/inward/record.url?scp=78249233850&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=78249233850&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0013798

DO - 10.1371/journal.pone.0013798

M3 - Article

VL - 5

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 11

M1 - e13798

ER -