Hierarchical role for transcription factors and chromatin structure in genome organization along adipogenesis

Avital Sarusi Portuguez, Michal Schwartz, Rasmus Siersbaek, Ronni Nielsen, Myong-Hee Sung, Susanne Mandrup, Tommy Kaplan, Ofir Hakim

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

The three dimensional folding of mammalian genomes is cell type specific and difficult to alter suggesting that it is an important component of gene regulation. However, given the multitude of chromatin-associating factors, the mechanisms driving the colocalization of active chromosomal domains and the role of this organization in regulating the transcription program in adipocytes are not clear. Analysis of genome-wide chromosomal associations revealed cell type-specific spatial clustering of adipogenic genes in 3T3-L1 cells. Time course analysis demonstrated that the adipogenic 'hub', sampled by PPARγ and Lpin1, undergoes orchestrated reorganization during adipogenesis. Coupling the dynamics of genome architecture with multiple chromatin datasets indicated that among all the transcription factors (TFs) tested, RXR is central to genome reorganization at the beginning of adipogenesis. Interestingly, at the end of differentiation, the adipogenic hub was shifted to an H3K27me3-repressive environment in conjunction with attenuation of gene transcription. We propose a stage-specific hierarchy for the activity of TFs contributing to the establishment of an adipogenic genome architecture that brings together the adipogenic genetic program. In addition, the repositioning of this network in a H3K27me3-rich environment at the end of differentiation may contribute to the stabilization of gene transcription levels and reduce the developmental plasticity of these specialized cells.

DATABASE: All sequence data reported in this paper have been deposited at GEO (http://www.ncbi.nlm.nih.gov/geo/) (GSE92475).

OriginalsprogEngelsk
TidsskriftF E B S Journal
Vol/bind284
Udgave nummer19
Sider (fra-til)3230-3244
ISSN1742-464X
DOI
StatusUdgivet - 2017

Fingeraftryk

Adipogenesis
3T3-L1 Cells
Genome-Wide Association Study
Adipocytes
Cluster Analysis

Citer dette

Sarusi Portuguez, Avital ; Schwartz, Michal ; Siersbaek, Rasmus ; Nielsen, Ronni ; Sung, Myong-Hee ; Mandrup, Susanne ; Kaplan, Tommy ; Hakim, Ofir. / Hierarchical role for transcription factors and chromatin structure in genome organization along adipogenesis. I: F E B S Journal. 2017 ; Bind 284, Nr. 19. s. 3230-3244.
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abstract = "The three dimensional folding of mammalian genomes is cell type specific and difficult to alter suggesting that it is an important component of gene regulation. However, given the multitude of chromatin-associating factors, the mechanisms driving the colocalization of active chromosomal domains and the role of this organization in regulating the transcription program in adipocytes are not clear. Analysis of genome-wide chromosomal associations revealed cell type-specific spatial clustering of adipogenic genes in 3T3-L1 cells. Time course analysis demonstrated that the adipogenic 'hub', sampled by PPARγ and Lpin1, undergoes orchestrated reorganization during adipogenesis. Coupling the dynamics of genome architecture with multiple chromatin datasets indicated that among all the transcription factors (TFs) tested, RXR is central to genome reorganization at the beginning of adipogenesis. Interestingly, at the end of differentiation, the adipogenic hub was shifted to an H3K27me3-repressive environment in conjunction with attenuation of gene transcription. We propose a stage-specific hierarchy for the activity of TFs contributing to the establishment of an adipogenic genome architecture that brings together the adipogenic genetic program. In addition, the repositioning of this network in a H3K27me3-rich environment at the end of differentiation may contribute to the stabilization of gene transcription levels and reduce the developmental plasticity of these specialized cells.DATABASE: All sequence data reported in this paper have been deposited at GEO (http://www.ncbi.nlm.nih.gov/geo/) (GSE92475).",
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Hierarchical role for transcription factors and chromatin structure in genome organization along adipogenesis. / Sarusi Portuguez, Avital; Schwartz, Michal; Siersbaek, Rasmus; Nielsen, Ronni; Sung, Myong-Hee; Mandrup, Susanne; Kaplan, Tommy; Hakim, Ofir.

I: F E B S Journal, Bind 284, Nr. 19, 2017, s. 3230-3244.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Hierarchical role for transcription factors and chromatin structure in genome organization along adipogenesis

AU - Sarusi Portuguez, Avital

AU - Schwartz, Michal

AU - Siersbaek, Rasmus

AU - Nielsen, Ronni

AU - Sung, Myong-Hee

AU - Mandrup, Susanne

AU - Kaplan, Tommy

AU - Hakim, Ofir

N1 - © 2017 Federation of European Biochemical Societies.

PY - 2017

Y1 - 2017

N2 - The three dimensional folding of mammalian genomes is cell type specific and difficult to alter suggesting that it is an important component of gene regulation. However, given the multitude of chromatin-associating factors, the mechanisms driving the colocalization of active chromosomal domains and the role of this organization in regulating the transcription program in adipocytes are not clear. Analysis of genome-wide chromosomal associations revealed cell type-specific spatial clustering of adipogenic genes in 3T3-L1 cells. Time course analysis demonstrated that the adipogenic 'hub', sampled by PPARγ and Lpin1, undergoes orchestrated reorganization during adipogenesis. Coupling the dynamics of genome architecture with multiple chromatin datasets indicated that among all the transcription factors (TFs) tested, RXR is central to genome reorganization at the beginning of adipogenesis. Interestingly, at the end of differentiation, the adipogenic hub was shifted to an H3K27me3-repressive environment in conjunction with attenuation of gene transcription. We propose a stage-specific hierarchy for the activity of TFs contributing to the establishment of an adipogenic genome architecture that brings together the adipogenic genetic program. In addition, the repositioning of this network in a H3K27me3-rich environment at the end of differentiation may contribute to the stabilization of gene transcription levels and reduce the developmental plasticity of these specialized cells.DATABASE: All sequence data reported in this paper have been deposited at GEO (http://www.ncbi.nlm.nih.gov/geo/) (GSE92475).

AB - The three dimensional folding of mammalian genomes is cell type specific and difficult to alter suggesting that it is an important component of gene regulation. However, given the multitude of chromatin-associating factors, the mechanisms driving the colocalization of active chromosomal domains and the role of this organization in regulating the transcription program in adipocytes are not clear. Analysis of genome-wide chromosomal associations revealed cell type-specific spatial clustering of adipogenic genes in 3T3-L1 cells. Time course analysis demonstrated that the adipogenic 'hub', sampled by PPARγ and Lpin1, undergoes orchestrated reorganization during adipogenesis. Coupling the dynamics of genome architecture with multiple chromatin datasets indicated that among all the transcription factors (TFs) tested, RXR is central to genome reorganization at the beginning of adipogenesis. Interestingly, at the end of differentiation, the adipogenic hub was shifted to an H3K27me3-repressive environment in conjunction with attenuation of gene transcription. We propose a stage-specific hierarchy for the activity of TFs contributing to the establishment of an adipogenic genome architecture that brings together the adipogenic genetic program. In addition, the repositioning of this network in a H3K27me3-rich environment at the end of differentiation may contribute to the stabilization of gene transcription levels and reduce the developmental plasticity of these specialized cells.DATABASE: All sequence data reported in this paper have been deposited at GEO (http://www.ncbi.nlm.nih.gov/geo/) (GSE92475).

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KW - CCAAT-Enhancer-Binding Proteins

KW - Cell Differentiation

KW - Chromatin

KW - Gene Expression Profiling

KW - Gene Expression Regulation

KW - Histones

KW - Interferon-gamma

KW - Mice

KW - Nuclear Proteins

KW - Organ Specificity

KW - PPAR gamma

KW - Phosphatidate Phosphatase

KW - Primary Cell Culture

KW - Retinoid X Receptors

KW - Signal Transduction

KW - Transcription, Genetic

KW - Journal Article

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DO - 10.1111/febs.14183

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VL - 284

SP - 3230

EP - 3244

JO - F E B S Journal

JF - F E B S Journal

SN - 1742-464X

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ER -