The role of Transposable Elements in shaping the combinatorial interaction of Transcription Factors

Alessandro Testori, Livia Caizzi, Santina Cutrupi, Olivier Friard, Michele De Bortoli, Davide Cora', Michele Caselle

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Background: In the last few years several studies have shown that Transposable Elements (TEs) in the human genome are significantly associated with Transcription Factor Binding Sites (TFBSs) and that in several cases their expansion within the genome led to a substantial rewiring of the regulatory network. Another important feature of the regulatory network which has been thoroughly studied is the combinatorial organization of transcriptional regulation. In this paper we combine these two observations and suggest that TEs, besides rewiring the network, also played a central role in the evolution of particular patterns of combinatorial gene regulation.Results: To address this issue we searched for TEs overlapping Estrogen Receptor α (ERα) binding peaks in two publicly available ChIP-seq datasets from the MCF7 cell line corresponding to different modalities of exposure to estrogen. We found a remarkable enrichment of a few specific classes of Transposons. Among these a prominent role was played by MIR (Mammalian Interspersed Repeats) transposons. These TEs underwent a dramatic expansion at the beginning of the mammalian radiation and then stabilized. We conjecture that the special affinity of ERα for the MIR class of TEs could be at the origin of the important role assumed by ERα in Mammalians. We then searched for TFBSs within the TEs overlapping ChIP-seq peaks. We found a strong enrichment of a few precise combinations of TFBS. In several cases the corresponding Transcription Factors (TFs) were known cofactors of ERα, thus supporting the idea of a co-regulatory role of TFBS within the same TE. Moreover, most of these correlations turned out to be strictly associated to specific classes of TEs thus suggesting the presence of a well-defined "transposon code" within the regulatory network.Conclusions: In this work we tried to shed light into the role of Transposable Elements (TEs) in shaping the regulatory network of higher eukaryotes. To test this idea we focused on a particular transcription factor: the Estrogen Receptor α (ERα) and we found that ERα preferentially targets a well defined set of TEs and that these TEs host combinations of transcriptional regulators involving several of known co-regulators of ERα. Moreover, a significant number of these TEs turned out to be conserved between human and mouse and located in the vicinity (and thus candidate to be regulators) of important estrogen-related genes.

Original languageEnglish
Article number400
JournalBMC Genomics
Volume13
Issue number1
DOIs
Publication statusPublished - Aug 16 2012

Fingerprint

DNA Transposable Elements
Transcription Factors
Estrogen Receptors
Binding Sites
Estrogens
MCF-7 Cells
Human Genome
Eukaryota
Genes

Keywords

  • ChIP-seq
  • Combinatorial interaction
  • ERα
  • Transcription factors
  • Transposable elements

ASJC Scopus subject areas

  • Biotechnology
  • Genetics

Cite this

The role of Transposable Elements in shaping the combinatorial interaction of Transcription Factors. / Testori, Alessandro; Caizzi, Livia; Cutrupi, Santina; Friard, Olivier; De Bortoli, Michele; Cora', Davide; Caselle, Michele.

In: BMC Genomics, Vol. 13, No. 1, 400, 16.08.2012.

Research output: Contribution to journalArticle

Testori, Alessandro ; Caizzi, Livia ; Cutrupi, Santina ; Friard, Olivier ; De Bortoli, Michele ; Cora', Davide ; Caselle, Michele. / The role of Transposable Elements in shaping the combinatorial interaction of Transcription Factors. In: BMC Genomics. 2012 ; Vol. 13, No. 1.
@article{970c824879484673bb4e804a3bb50cb3,
title = "The role of Transposable Elements in shaping the combinatorial interaction of Transcription Factors",
abstract = "Background: In the last few years several studies have shown that Transposable Elements (TEs) in the human genome are significantly associated with Transcription Factor Binding Sites (TFBSs) and that in several cases their expansion within the genome led to a substantial rewiring of the regulatory network. Another important feature of the regulatory network which has been thoroughly studied is the combinatorial organization of transcriptional regulation. In this paper we combine these two observations and suggest that TEs, besides rewiring the network, also played a central role in the evolution of particular patterns of combinatorial gene regulation.Results: To address this issue we searched for TEs overlapping Estrogen Receptor α (ERα) binding peaks in two publicly available ChIP-seq datasets from the MCF7 cell line corresponding to different modalities of exposure to estrogen. We found a remarkable enrichment of a few specific classes of Transposons. Among these a prominent role was played by MIR (Mammalian Interspersed Repeats) transposons. These TEs underwent a dramatic expansion at the beginning of the mammalian radiation and then stabilized. We conjecture that the special affinity of ERα for the MIR class of TEs could be at the origin of the important role assumed by ERα in Mammalians. We then searched for TFBSs within the TEs overlapping ChIP-seq peaks. We found a strong enrichment of a few precise combinations of TFBS. In several cases the corresponding Transcription Factors (TFs) were known cofactors of ERα, thus supporting the idea of a co-regulatory role of TFBS within the same TE. Moreover, most of these correlations turned out to be strictly associated to specific classes of TEs thus suggesting the presence of a well-defined {"}transposon code{"} within the regulatory network.Conclusions: In this work we tried to shed light into the role of Transposable Elements (TEs) in shaping the regulatory network of higher eukaryotes. To test this idea we focused on a particular transcription factor: the Estrogen Receptor α (ERα) and we found that ERα preferentially targets a well defined set of TEs and that these TEs host combinations of transcriptional regulators involving several of known co-regulators of ERα. Moreover, a significant number of these TEs turned out to be conserved between human and mouse and located in the vicinity (and thus candidate to be regulators) of important estrogen-related genes.",
keywords = "ChIP-seq, Combinatorial interaction, ERα, Transcription factors, Transposable elements",
author = "Alessandro Testori and Livia Caizzi and Santina Cutrupi and Olivier Friard and {De Bortoli}, Michele and Davide Cora' and Michele Caselle",
year = "2012",
month = "8",
day = "16",
doi = "10.1186/1471-2164-13-400",
language = "English",
volume = "13",
journal = "BMC Genomics",
issn = "1471-2164",
publisher = "BioMed Central",
number = "1",

}

TY - JOUR

T1 - The role of Transposable Elements in shaping the combinatorial interaction of Transcription Factors

AU - Testori, Alessandro

AU - Caizzi, Livia

AU - Cutrupi, Santina

AU - Friard, Olivier

AU - De Bortoli, Michele

AU - Cora', Davide

AU - Caselle, Michele

PY - 2012/8/16

Y1 - 2012/8/16

N2 - Background: In the last few years several studies have shown that Transposable Elements (TEs) in the human genome are significantly associated with Transcription Factor Binding Sites (TFBSs) and that in several cases their expansion within the genome led to a substantial rewiring of the regulatory network. Another important feature of the regulatory network which has been thoroughly studied is the combinatorial organization of transcriptional regulation. In this paper we combine these two observations and suggest that TEs, besides rewiring the network, also played a central role in the evolution of particular patterns of combinatorial gene regulation.Results: To address this issue we searched for TEs overlapping Estrogen Receptor α (ERα) binding peaks in two publicly available ChIP-seq datasets from the MCF7 cell line corresponding to different modalities of exposure to estrogen. We found a remarkable enrichment of a few specific classes of Transposons. Among these a prominent role was played by MIR (Mammalian Interspersed Repeats) transposons. These TEs underwent a dramatic expansion at the beginning of the mammalian radiation and then stabilized. We conjecture that the special affinity of ERα for the MIR class of TEs could be at the origin of the important role assumed by ERα in Mammalians. We then searched for TFBSs within the TEs overlapping ChIP-seq peaks. We found a strong enrichment of a few precise combinations of TFBS. In several cases the corresponding Transcription Factors (TFs) were known cofactors of ERα, thus supporting the idea of a co-regulatory role of TFBS within the same TE. Moreover, most of these correlations turned out to be strictly associated to specific classes of TEs thus suggesting the presence of a well-defined "transposon code" within the regulatory network.Conclusions: In this work we tried to shed light into the role of Transposable Elements (TEs) in shaping the regulatory network of higher eukaryotes. To test this idea we focused on a particular transcription factor: the Estrogen Receptor α (ERα) and we found that ERα preferentially targets a well defined set of TEs and that these TEs host combinations of transcriptional regulators involving several of known co-regulators of ERα. Moreover, a significant number of these TEs turned out to be conserved between human and mouse and located in the vicinity (and thus candidate to be regulators) of important estrogen-related genes.

AB - Background: In the last few years several studies have shown that Transposable Elements (TEs) in the human genome are significantly associated with Transcription Factor Binding Sites (TFBSs) and that in several cases their expansion within the genome led to a substantial rewiring of the regulatory network. Another important feature of the regulatory network which has been thoroughly studied is the combinatorial organization of transcriptional regulation. In this paper we combine these two observations and suggest that TEs, besides rewiring the network, also played a central role in the evolution of particular patterns of combinatorial gene regulation.Results: To address this issue we searched for TEs overlapping Estrogen Receptor α (ERα) binding peaks in two publicly available ChIP-seq datasets from the MCF7 cell line corresponding to different modalities of exposure to estrogen. We found a remarkable enrichment of a few specific classes of Transposons. Among these a prominent role was played by MIR (Mammalian Interspersed Repeats) transposons. These TEs underwent a dramatic expansion at the beginning of the mammalian radiation and then stabilized. We conjecture that the special affinity of ERα for the MIR class of TEs could be at the origin of the important role assumed by ERα in Mammalians. We then searched for TFBSs within the TEs overlapping ChIP-seq peaks. We found a strong enrichment of a few precise combinations of TFBS. In several cases the corresponding Transcription Factors (TFs) were known cofactors of ERα, thus supporting the idea of a co-regulatory role of TFBS within the same TE. Moreover, most of these correlations turned out to be strictly associated to specific classes of TEs thus suggesting the presence of a well-defined "transposon code" within the regulatory network.Conclusions: In this work we tried to shed light into the role of Transposable Elements (TEs) in shaping the regulatory network of higher eukaryotes. To test this idea we focused on a particular transcription factor: the Estrogen Receptor α (ERα) and we found that ERα preferentially targets a well defined set of TEs and that these TEs host combinations of transcriptional regulators involving several of known co-regulators of ERα. Moreover, a significant number of these TEs turned out to be conserved between human and mouse and located in the vicinity (and thus candidate to be regulators) of important estrogen-related genes.

KW - ChIP-seq

KW - Combinatorial interaction

KW - ERα

KW - Transcription factors

KW - Transposable elements

UR - http://www.scopus.com/inward/record.url?scp=84864938012&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84864938012&partnerID=8YFLogxK

U2 - 10.1186/1471-2164-13-400

DO - 10.1186/1471-2164-13-400

M3 - Article

C2 - 22897927

AN - SCOPUS:84864938012

VL - 13

JO - BMC Genomics

JF - BMC Genomics

SN - 1471-2164

IS - 1

M1 - 400

ER -