Genome-wide targeting of the epigenetic regulatory protein ctcf to gene promoters by the transcription factor TFII-I

Rodrigo Peñ A-Hernández, Maud Marques, Khalid Hilmi, Teijun Zhao, Amine Saad, Moulay A. Alaoui-Jamali, Sonia V.Del Rincon, Todd Ashworth, Ananda L. Roy, Beverly Emerson, Michael Witcher

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

CCCTC-binding factor (CTCF) is a key regulator of nuclear chromatin structure and gene regulation. The impact of CTCF on transcriptional output is highly varied, ranging from repression to transcriptional pausing and transactivation. The multifunctional nature of CTCF may be directed solely through remodeling chromatin architecture. However, another hypothesis is that the multifunctional nature of CTCF is mediated, in part, through differential association with protein partners having unique functions. Consistent with this hypothesis, our mass spectrometry analyses of CTCF interacting partners reveal a previously undefined association with the transcription factor general transcription factor II-I (TFII-I). Biochemical fractionation of CTCF indicates that a distinct CTCF complex incorporating TFII-I is assembled on DNA. Unexpectedly, we found that the interaction between CTCF and TFII-I is essential for directing CTCF to the promoter proximal regulatory regions of target genes across the genome, particularly at genes involved in metabolism. At genes coregulated by CTCF and TFII-I, we find knockdown of TFII-I results in diminished CTCF binding, lack of cyclin-dependent kinase 8 (CDK8) recruitment, and an attenuation of RNA polymerase II phosphorylation at serine 5. Phenotypically, knockdown of TFII-I alters the cellular response to metabolic stress. Our data indicate that TFII-I directs CTCF binding to target genes, and in turn the two proteins cooperate to recruit CDK8 and enhance transcription initiation. CTCF TFII-I CDK8.

Original languageEnglish (US)
Pages (from-to)E677-E686
JournalProceedings of the National Academy of Sciences of the United States of America
Volume112
Issue number7
DOIs
StatePublished - Feb 17 2015
Externally publishedYes

Fingerprint

Epigenomics
Transcription Factors
Cyclin-Dependent Kinase 8
Genome
Genes
Proteins
General Transcription Factors
Physiological Stress
Chromatin Assembly and Disassembly
RNA Polymerase II
Nucleic Acid Regulatory Sequences
Serine
Transcriptional Activation
Chromatin
Mass Spectrometry
Phosphorylation
DNA

ASJC Scopus subject areas

  • General

Cite this

Genome-wide targeting of the epigenetic regulatory protein ctcf to gene promoters by the transcription factor TFII-I. / Peñ A-Hernández, Rodrigo; Marques, Maud; Hilmi, Khalid; Zhao, Teijun; Saad, Amine; Alaoui-Jamali, Moulay A.; Rincon, Sonia V.Del; Ashworth, Todd; Roy, Ananda L.; Emerson, Beverly; Witcher, Michael.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 112, No. 7, 17.02.2015, p. E677-E686.

Research output: Contribution to journalArticle

Peñ A-Hernández, R, Marques, M, Hilmi, K, Zhao, T, Saad, A, Alaoui-Jamali, MA, Rincon, SVD, Ashworth, T, Roy, AL, Emerson, B & Witcher, M 2015, 'Genome-wide targeting of the epigenetic regulatory protein ctcf to gene promoters by the transcription factor TFII-I', Proceedings of the National Academy of Sciences of the United States of America, vol. 112, no. 7, pp. E677-E686. https://doi.org/10.1073/pnas.1416674112
Peñ A-Hernández, Rodrigo ; Marques, Maud ; Hilmi, Khalid ; Zhao, Teijun ; Saad, Amine ; Alaoui-Jamali, Moulay A. ; Rincon, Sonia V.Del ; Ashworth, Todd ; Roy, Ananda L. ; Emerson, Beverly ; Witcher, Michael. / Genome-wide targeting of the epigenetic regulatory protein ctcf to gene promoters by the transcription factor TFII-I. In: Proceedings of the National Academy of Sciences of the United States of America. 2015 ; Vol. 112, No. 7. pp. E677-E686.
@article{741cb3aebf834bfc88540543433918ab,
title = "Genome-wide targeting of the epigenetic regulatory protein ctcf to gene promoters by the transcription factor TFII-I",
abstract = "CCCTC-binding factor (CTCF) is a key regulator of nuclear chromatin structure and gene regulation. The impact of CTCF on transcriptional output is highly varied, ranging from repression to transcriptional pausing and transactivation. The multifunctional nature of CTCF may be directed solely through remodeling chromatin architecture. However, another hypothesis is that the multifunctional nature of CTCF is mediated, in part, through differential association with protein partners having unique functions. Consistent with this hypothesis, our mass spectrometry analyses of CTCF interacting partners reveal a previously undefined association with the transcription factor general transcription factor II-I (TFII-I). Biochemical fractionation of CTCF indicates that a distinct CTCF complex incorporating TFII-I is assembled on DNA. Unexpectedly, we found that the interaction between CTCF and TFII-I is essential for directing CTCF to the promoter proximal regulatory regions of target genes across the genome, particularly at genes involved in metabolism. At genes coregulated by CTCF and TFII-I, we find knockdown of TFII-I results in diminished CTCF binding, lack of cyclin-dependent kinase 8 (CDK8) recruitment, and an attenuation of RNA polymerase II phosphorylation at serine 5. Phenotypically, knockdown of TFII-I alters the cellular response to metabolic stress. Our data indicate that TFII-I directs CTCF binding to target genes, and in turn the two proteins cooperate to recruit CDK8 and enhance transcription initiation. CTCF TFII-I CDK8.",
author = "{Pe{\~n} A-Hern{\'a}ndez}, Rodrigo and Maud Marques and Khalid Hilmi and Teijun Zhao and Amine Saad and Alaoui-Jamali, {Moulay A.} and Rincon, {Sonia V.Del} and Todd Ashworth and Roy, {Ananda L.} and Beverly Emerson and Michael Witcher",
year = "2015",
month = "2",
day = "17",
doi = "10.1073/pnas.1416674112",
language = "English (US)",
volume = "112",
pages = "E677--E686",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "7",

}

TY - JOUR

T1 - Genome-wide targeting of the epigenetic regulatory protein ctcf to gene promoters by the transcription factor TFII-I

AU - Peñ A-Hernández, Rodrigo

AU - Marques, Maud

AU - Hilmi, Khalid

AU - Zhao, Teijun

AU - Saad, Amine

AU - Alaoui-Jamali, Moulay A.

AU - Rincon, Sonia V.Del

AU - Ashworth, Todd

AU - Roy, Ananda L.

AU - Emerson, Beverly

AU - Witcher, Michael

PY - 2015/2/17

Y1 - 2015/2/17

N2 - CCCTC-binding factor (CTCF) is a key regulator of nuclear chromatin structure and gene regulation. The impact of CTCF on transcriptional output is highly varied, ranging from repression to transcriptional pausing and transactivation. The multifunctional nature of CTCF may be directed solely through remodeling chromatin architecture. However, another hypothesis is that the multifunctional nature of CTCF is mediated, in part, through differential association with protein partners having unique functions. Consistent with this hypothesis, our mass spectrometry analyses of CTCF interacting partners reveal a previously undefined association with the transcription factor general transcription factor II-I (TFII-I). Biochemical fractionation of CTCF indicates that a distinct CTCF complex incorporating TFII-I is assembled on DNA. Unexpectedly, we found that the interaction between CTCF and TFII-I is essential for directing CTCF to the promoter proximal regulatory regions of target genes across the genome, particularly at genes involved in metabolism. At genes coregulated by CTCF and TFII-I, we find knockdown of TFII-I results in diminished CTCF binding, lack of cyclin-dependent kinase 8 (CDK8) recruitment, and an attenuation of RNA polymerase II phosphorylation at serine 5. Phenotypically, knockdown of TFII-I alters the cellular response to metabolic stress. Our data indicate that TFII-I directs CTCF binding to target genes, and in turn the two proteins cooperate to recruit CDK8 and enhance transcription initiation. CTCF TFII-I CDK8.

AB - CCCTC-binding factor (CTCF) is a key regulator of nuclear chromatin structure and gene regulation. The impact of CTCF on transcriptional output is highly varied, ranging from repression to transcriptional pausing and transactivation. The multifunctional nature of CTCF may be directed solely through remodeling chromatin architecture. However, another hypothesis is that the multifunctional nature of CTCF is mediated, in part, through differential association with protein partners having unique functions. Consistent with this hypothesis, our mass spectrometry analyses of CTCF interacting partners reveal a previously undefined association with the transcription factor general transcription factor II-I (TFII-I). Biochemical fractionation of CTCF indicates that a distinct CTCF complex incorporating TFII-I is assembled on DNA. Unexpectedly, we found that the interaction between CTCF and TFII-I is essential for directing CTCF to the promoter proximal regulatory regions of target genes across the genome, particularly at genes involved in metabolism. At genes coregulated by CTCF and TFII-I, we find knockdown of TFII-I results in diminished CTCF binding, lack of cyclin-dependent kinase 8 (CDK8) recruitment, and an attenuation of RNA polymerase II phosphorylation at serine 5. Phenotypically, knockdown of TFII-I alters the cellular response to metabolic stress. Our data indicate that TFII-I directs CTCF binding to target genes, and in turn the two proteins cooperate to recruit CDK8 and enhance transcription initiation. CTCF TFII-I CDK8.

UR - http://www.scopus.com/inward/record.url?scp=84923169821&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84923169821&partnerID=8YFLogxK

U2 - 10.1073/pnas.1416674112

DO - 10.1073/pnas.1416674112

M3 - Article

C2 - 25646466

AN - SCOPUS:84923169821

VL - 112

SP - E677-E686

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 7

ER -