Dynamic Rewiring of Promoter-Anchored Chromatin Loops during Adipocyte Differentiation

Rasmus Siersbæk, Jesper Grud Skat Madsen, Biola Maria Javierre, Ronni Nielsen, Emilie Kristine Bagge, Jonathan Cairns, Steven William Wingett, Sofie Traynor, Mikhail Spivakov, Peter Fraser, Susanne Mandrup

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

Interactions between transcriptional promoters and their distal regulatory elements play an important role in transcriptional regulation; however, the extent to which these interactions are subject to rapid modulations in response to signals is unknown. Here, we use promoter capture Hi-C to demonstrate a rapid reorganization of promoter-anchored chromatin loops within 4 hr after inducing differentiation of 3T3-L1 preadipocytes. The establishment of new promoter-enhancer loops is tightly coupled to activation of poised (histone H3 lysine 4 mono- and dimethylated) enhancers, as evidenced by the acquisition of histone H3 lysine 27 acetylation and the binding of MED1, SMC1, and P300 proteins to these regions, as well as to activation of target genes. Intriguingly, formation of loops connecting activated enhancers and promoters is also associated with extensive recruitment of corepressors such as NCoR and HDACs, indicating that this class of coregulators may play a previously unrecognized role during enhancer activation.

OriginalsprogEngelsk
TidsskriftMolecular Cell
Vol/bind66
Udgave nummer3
Sider (fra-til)420-435.e5
ISSN1097-2765
DOI
StatusUdgivet - 2017

Fingeraftryk

Adipocytes
Histones
Lysine
Acetylation
Transcriptional Activation

Citer dette

Siersbæk, Rasmus ; Madsen, Jesper Grud Skat ; Javierre, Biola Maria ; Nielsen, Ronni ; Bagge, Emilie Kristine ; Cairns, Jonathan ; Wingett, Steven William ; Traynor, Sofie ; Spivakov, Mikhail ; Fraser, Peter ; Mandrup, Susanne. / Dynamic Rewiring of Promoter-Anchored Chromatin Loops during Adipocyte Differentiation. I: Molecular Cell. 2017 ; Bind 66, Nr. 3. s. 420-435.e5.
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abstract = "Interactions between transcriptional promoters and their distal regulatory elements play an important role in transcriptional regulation; however, the extent to which these interactions are subject to rapid modulations in response to signals is unknown. Here, we use promoter capture Hi-C to demonstrate a rapid reorganization of promoter-anchored chromatin loops within 4 hr after inducing differentiation of 3T3-L1 preadipocytes. The establishment of new promoter-enhancer loops is tightly coupled to activation of poised (histone H3 lysine 4 mono- and dimethylated) enhancers, as evidenced by the acquisition of histone H3 lysine 27 acetylation and the binding of MED1, SMC1, and P300 proteins to these regions, as well as to activation of target genes. Intriguingly, formation of loops connecting activated enhancers and promoters is also associated with extensive recruitment of corepressors such as NCoR and HDACs, indicating that this class of coregulators may play a previously unrecognized role during enhancer activation.",
keywords = "3T3-L1 Cells, Adipocytes, Adipogenesis, Animals, Cell Cycle Proteins, Chromatin, Chromatin Assembly and Disassembly, Chromatin Immunoprecipitation, Chromosomal Proteins, Non-Histone, E1A-Associated p300 Protein, Enhancer Elements, Genetic, Mediator Complex Subunit 1, Mice, Nucleic Acid Conformation, Promoter Regions, Genetic, RNA, Messenger, Sequence Analysis, RNA, Time Factors, Transcription, Genetic, Transcriptional Activation, Journal Article",
author = "Rasmus Siersb{\ae}k and Madsen, {Jesper Grud Skat} and Javierre, {Biola Maria} and Ronni Nielsen and Bagge, {Emilie Kristine} and Jonathan Cairns and Wingett, {Steven William} and Sofie Traynor and Mikhail Spivakov and Peter Fraser and Susanne Mandrup",
note = "Copyright {\circledC} 2017 Elsevier Inc. All rights reserved.",
year = "2017",
doi = "10.1016/j.molcel.2017.04.010",
language = "English",
volume = "66",
pages = "420--435.e5",
journal = "Molecular Cell",
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Dynamic Rewiring of Promoter-Anchored Chromatin Loops during Adipocyte Differentiation. / Siersbæk, Rasmus; Madsen, Jesper Grud Skat; Javierre, Biola Maria; Nielsen, Ronni; Bagge, Emilie Kristine; Cairns, Jonathan; Wingett, Steven William; Traynor, Sofie; Spivakov, Mikhail; Fraser, Peter; Mandrup, Susanne.

I: Molecular Cell, Bind 66, Nr. 3, 2017, s. 420-435.e5.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Dynamic Rewiring of Promoter-Anchored Chromatin Loops during Adipocyte Differentiation

AU - Siersbæk, Rasmus

AU - Madsen, Jesper Grud Skat

AU - Javierre, Biola Maria

AU - Nielsen, Ronni

AU - Bagge, Emilie Kristine

AU - Cairns, Jonathan

AU - Wingett, Steven William

AU - Traynor, Sofie

AU - Spivakov, Mikhail

AU - Fraser, Peter

AU - Mandrup, Susanne

N1 - Copyright © 2017 Elsevier Inc. All rights reserved.

PY - 2017

Y1 - 2017

N2 - Interactions between transcriptional promoters and their distal regulatory elements play an important role in transcriptional regulation; however, the extent to which these interactions are subject to rapid modulations in response to signals is unknown. Here, we use promoter capture Hi-C to demonstrate a rapid reorganization of promoter-anchored chromatin loops within 4 hr after inducing differentiation of 3T3-L1 preadipocytes. The establishment of new promoter-enhancer loops is tightly coupled to activation of poised (histone H3 lysine 4 mono- and dimethylated) enhancers, as evidenced by the acquisition of histone H3 lysine 27 acetylation and the binding of MED1, SMC1, and P300 proteins to these regions, as well as to activation of target genes. Intriguingly, formation of loops connecting activated enhancers and promoters is also associated with extensive recruitment of corepressors such as NCoR and HDACs, indicating that this class of coregulators may play a previously unrecognized role during enhancer activation.

AB - Interactions between transcriptional promoters and their distal regulatory elements play an important role in transcriptional regulation; however, the extent to which these interactions are subject to rapid modulations in response to signals is unknown. Here, we use promoter capture Hi-C to demonstrate a rapid reorganization of promoter-anchored chromatin loops within 4 hr after inducing differentiation of 3T3-L1 preadipocytes. The establishment of new promoter-enhancer loops is tightly coupled to activation of poised (histone H3 lysine 4 mono- and dimethylated) enhancers, as evidenced by the acquisition of histone H3 lysine 27 acetylation and the binding of MED1, SMC1, and P300 proteins to these regions, as well as to activation of target genes. Intriguingly, formation of loops connecting activated enhancers and promoters is also associated with extensive recruitment of corepressors such as NCoR and HDACs, indicating that this class of coregulators may play a previously unrecognized role during enhancer activation.

KW - 3T3-L1 Cells

KW - Adipocytes

KW - Adipogenesis

KW - Animals

KW - Cell Cycle Proteins

KW - Chromatin

KW - Chromatin Assembly and Disassembly

KW - Chromatin Immunoprecipitation

KW - Chromosomal Proteins, Non-Histone

KW - E1A-Associated p300 Protein

KW - Enhancer Elements, Genetic

KW - Mediator Complex Subunit 1

KW - Mice

KW - Nucleic Acid Conformation

KW - Promoter Regions, Genetic

KW - RNA, Messenger

KW - Sequence Analysis, RNA

KW - Time Factors

KW - Transcription, Genetic

KW - Transcriptional Activation

KW - Journal Article

U2 - 10.1016/j.molcel.2017.04.010

DO - 10.1016/j.molcel.2017.04.010

M3 - Journal article

VL - 66

SP - 420-435.e5

JO - Molecular Cell

JF - Molecular Cell

SN - 1097-2765

IS - 3

ER -