Interactome maps of mouse gene regulatory domains reveal basic principles of transcriptional regulation

Kyong-Rim Kieffer-Kwon, Zhonghui Tang, Ewy Mathe, Jason Qian, Myong-Hee Sung, Guoliang Li, Wolfgang Resch, Songjoon Baek, Nathanael Pruett, Lars Grøntved, Laura Vian, Steevenson Nelson, Hossein Zare, Ofir Hakim, Deepak Reyon, Arito Yamane, Hirotaka Nakahashi, Alexander L Kovalchuk, Jizhong Zou, J Keith JoungVittorio Sartorelli, Chia-Lin Wei, Xiaoan Ruan, Gordon L Hager, Yijun Ruan, Rafael Casellas

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

A key finding of the ENCODE project is that the enhancer landscape of mammalian cells undergoes marked alterations during ontogeny. However, the nature and extent of these changes are unclear. As part of the NIH Mouse Regulome Project, we here combined DNaseI hypersensitivity, ChIP-seq, and ChIA-PET technologies to map the promoter-enhancer interactomes of pluripotent ES cells and differentiated B lymphocytes. We confirm that enhancer usage varies widely across tissues. Unexpectedly, we find that this feature extends to broadly transcribed genes, including Myc and Pim1 cell-cycle regulators, which associate with an entirely different set of enhancers in ES and B cells. By means of high-resolution CpG methylomes, genome editing, and digital footprinting, we show that these enhancers recruit lineage-determining factors. Furthermore, we demonstrate that the turning on and off of enhancers during development correlates with promoter activity. We propose that organisms rely on a dynamic enhancer landscape to control basic cellular functions in a tissue-specific manner.

Original languageEnglish
JournalCell
Volume155
Issue number7
Pages (from-to)1507-20
ISSN0092-8674
DOIs
Publication statusPublished - 2013

Fingerprint

Genes
Cells
myc Genes
Tissue
Cell Cycle
Hypersensitivity
Lymphocytes
Gene Editing

Keywords

  • Animals
  • B-Lymphocytes
  • Cell Lineage
  • Cells, Cultured
  • CpG Islands
  • DNA Methylation
  • Embryonic Stem Cells
  • Enhancer Elements, Genetic
  • Gene Expression Regulation, Developmental
  • Genetic Techniques
  • Mice
  • Organ Specificity
  • Promoter Regions, Genetic
  • RNA, Long Noncoding
  • Regulon
  • Transcription Factors
  • Transcription, Genetic

Cite this

Kieffer-Kwon, K-R., Tang, Z., Mathe, E., Qian, J., Sung, M-H., Li, G., ... Casellas, R. (2013). Interactome maps of mouse gene regulatory domains reveal basic principles of transcriptional regulation. Cell, 155(7), 1507-20. https://doi.org/10.1016/j.cell.2013.11.039
Kieffer-Kwon, Kyong-Rim ; Tang, Zhonghui ; Mathe, Ewy ; Qian, Jason ; Sung, Myong-Hee ; Li, Guoliang ; Resch, Wolfgang ; Baek, Songjoon ; Pruett, Nathanael ; Grøntved, Lars ; Vian, Laura ; Nelson, Steevenson ; Zare, Hossein ; Hakim, Ofir ; Reyon, Deepak ; Yamane, Arito ; Nakahashi, Hirotaka ; Kovalchuk, Alexander L ; Zou, Jizhong ; Joung, J Keith ; Sartorelli, Vittorio ; Wei, Chia-Lin ; Ruan, Xiaoan ; Hager, Gordon L ; Ruan, Yijun ; Casellas, Rafael. / Interactome maps of mouse gene regulatory domains reveal basic principles of transcriptional regulation. In: Cell. 2013 ; Vol. 155, No. 7. pp. 1507-20.
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abstract = "A key finding of the ENCODE project is that the enhancer landscape of mammalian cells undergoes marked alterations during ontogeny. However, the nature and extent of these changes are unclear. As part of the NIH Mouse Regulome Project, we here combined DNaseI hypersensitivity, ChIP-seq, and ChIA-PET technologies to map the promoter-enhancer interactomes of pluripotent ES cells and differentiated B lymphocytes. We confirm that enhancer usage varies widely across tissues. Unexpectedly, we find that this feature extends to broadly transcribed genes, including Myc and Pim1 cell-cycle regulators, which associate with an entirely different set of enhancers in ES and B cells. By means of high-resolution CpG methylomes, genome editing, and digital footprinting, we show that these enhancers recruit lineage-determining factors. Furthermore, we demonstrate that the turning on and off of enhancers during development correlates with promoter activity. We propose that organisms rely on a dynamic enhancer landscape to control basic cellular functions in a tissue-specific manner.",
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author = "Kyong-Rim Kieffer-Kwon and Zhonghui Tang and Ewy Mathe and Jason Qian and Myong-Hee Sung and Guoliang Li and Wolfgang Resch and Songjoon Baek and Nathanael Pruett and Lars Gr{\o}ntved and Laura Vian and Steevenson Nelson and Hossein Zare and Ofir Hakim and Deepak Reyon and Arito Yamane and Hirotaka Nakahashi and Kovalchuk, {Alexander L} and Jizhong Zou and Joung, {J Keith} and Vittorio Sartorelli and Chia-Lin Wei and Xiaoan Ruan and Hager, {Gordon L} and Yijun Ruan and Rafael Casellas",
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pages = "1507--20",
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Kieffer-Kwon, K-R, Tang, Z, Mathe, E, Qian, J, Sung, M-H, Li, G, Resch, W, Baek, S, Pruett, N, Grøntved, L, Vian, L, Nelson, S, Zare, H, Hakim, O, Reyon, D, Yamane, A, Nakahashi, H, Kovalchuk, AL, Zou, J, Joung, JK, Sartorelli, V, Wei, C-L, Ruan, X, Hager, GL, Ruan, Y & Casellas, R 2013, 'Interactome maps of mouse gene regulatory domains reveal basic principles of transcriptional regulation', Cell, vol. 155, no. 7, pp. 1507-20. https://doi.org/10.1016/j.cell.2013.11.039

Interactome maps of mouse gene regulatory domains reveal basic principles of transcriptional regulation. / Kieffer-Kwon, Kyong-Rim; Tang, Zhonghui; Mathe, Ewy; Qian, Jason; Sung, Myong-Hee; Li, Guoliang; Resch, Wolfgang; Baek, Songjoon; Pruett, Nathanael; Grøntved, Lars; Vian, Laura; Nelson, Steevenson; Zare, Hossein; Hakim, Ofir; Reyon, Deepak; Yamane, Arito; Nakahashi, Hirotaka; Kovalchuk, Alexander L; Zou, Jizhong; Joung, J Keith; Sartorelli, Vittorio; Wei, Chia-Lin; Ruan, Xiaoan; Hager, Gordon L; Ruan, Yijun; Casellas, Rafael.

In: Cell, Vol. 155, No. 7, 2013, p. 1507-20.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - Interactome maps of mouse gene regulatory domains reveal basic principles of transcriptional regulation

AU - Kieffer-Kwon, Kyong-Rim

AU - Tang, Zhonghui

AU - Mathe, Ewy

AU - Qian, Jason

AU - Sung, Myong-Hee

AU - Li, Guoliang

AU - Resch, Wolfgang

AU - Baek, Songjoon

AU - Pruett, Nathanael

AU - Grøntved, Lars

AU - Vian, Laura

AU - Nelson, Steevenson

AU - Zare, Hossein

AU - Hakim, Ofir

AU - Reyon, Deepak

AU - Yamane, Arito

AU - Nakahashi, Hirotaka

AU - Kovalchuk, Alexander L

AU - Zou, Jizhong

AU - Joung, J Keith

AU - Sartorelli, Vittorio

AU - Wei, Chia-Lin

AU - Ruan, Xiaoan

AU - Hager, Gordon L

AU - Ruan, Yijun

AU - Casellas, Rafael

N1 - Copyright © 2013 Elsevier Inc. All rights reserved.

PY - 2013

Y1 - 2013

N2 - A key finding of the ENCODE project is that the enhancer landscape of mammalian cells undergoes marked alterations during ontogeny. However, the nature and extent of these changes are unclear. As part of the NIH Mouse Regulome Project, we here combined DNaseI hypersensitivity, ChIP-seq, and ChIA-PET technologies to map the promoter-enhancer interactomes of pluripotent ES cells and differentiated B lymphocytes. We confirm that enhancer usage varies widely across tissues. Unexpectedly, we find that this feature extends to broadly transcribed genes, including Myc and Pim1 cell-cycle regulators, which associate with an entirely different set of enhancers in ES and B cells. By means of high-resolution CpG methylomes, genome editing, and digital footprinting, we show that these enhancers recruit lineage-determining factors. Furthermore, we demonstrate that the turning on and off of enhancers during development correlates with promoter activity. We propose that organisms rely on a dynamic enhancer landscape to control basic cellular functions in a tissue-specific manner.

AB - A key finding of the ENCODE project is that the enhancer landscape of mammalian cells undergoes marked alterations during ontogeny. However, the nature and extent of these changes are unclear. As part of the NIH Mouse Regulome Project, we here combined DNaseI hypersensitivity, ChIP-seq, and ChIA-PET technologies to map the promoter-enhancer interactomes of pluripotent ES cells and differentiated B lymphocytes. We confirm that enhancer usage varies widely across tissues. Unexpectedly, we find that this feature extends to broadly transcribed genes, including Myc and Pim1 cell-cycle regulators, which associate with an entirely different set of enhancers in ES and B cells. By means of high-resolution CpG methylomes, genome editing, and digital footprinting, we show that these enhancers recruit lineage-determining factors. Furthermore, we demonstrate that the turning on and off of enhancers during development correlates with promoter activity. We propose that organisms rely on a dynamic enhancer landscape to control basic cellular functions in a tissue-specific manner.

KW - Animals

KW - B-Lymphocytes

KW - Cell Lineage

KW - Cells, Cultured

KW - CpG Islands

KW - DNA Methylation

KW - Embryonic Stem Cells

KW - Enhancer Elements, Genetic

KW - Gene Expression Regulation, Developmental

KW - Genetic Techniques

KW - Mice

KW - Organ Specificity

KW - Promoter Regions, Genetic

KW - RNA, Long Noncoding

KW - Regulon

KW - Transcription Factors

KW - Transcription, Genetic

U2 - 10.1016/j.cell.2013.11.039

DO - 10.1016/j.cell.2013.11.039

M3 - Journal article

C2 - 24360274

VL - 155

SP - 1507

EP - 1520

JO - Cell

JF - Cell

SN - 0092-8674

IS - 7

ER -