Peroxisome proliferator-activated receptor gamma recruits the positive transcription elongation factor b complex to activate transcription and promote adipogenesis.

Irena Iankova; Rasmus K Petersen; Jean-Sébastien Annicotte; Carine Chavey; Jacob B Hansen; Irina Kratchmarova; David Sarruf; Monsef Benkirane; Karsten Kristiansen; Lluis Fajas

doi:10.1210/me.2005-0222

Peroxisome proliferator-activated receptor gamma recruits the positive transcription elongation factor b complex to activate transcription and promote adipogenesis.

Irena Iankova, Rasmus K Petersen, Jean-Sébastien Annicotte, Carine Chavey, Jacob B Hansen, Irina Kratchmarova, David Sarruf, Monsef Benkirane, Karsten Kristiansen, Lluis Fajas

Department of Biomedical Sciences

81 Citations (Scopus)

Abstract

Positive transcription elongation factor b (P-TEFb) phosphorylates the C-terminal domain of RNA polymerase II, facilitating transcriptional elongation. In addition to its participation in general transcription, P-TEFb is recruited to specific promoters by some transcription factors such as c-Myc or MyoD. The P-TEFb complex is composed of a cyclin-dependent kinase (cdk9) subunit and a regulatory partner (cyclin T1, cyclin T2, or cyclin K). Because cdk9 has been shown to participate in differentiation processes, such as muscle cell differentiation, we studied a possible role of cdk9 in adipogenesis. In this study we show that the expression of the cdk9 p55 isoform is highly regulated during 3T3-L1 adipocyte differentiation at RNA and protein levels. Furthermore, cdk9, as well as cyclin T1 and cyclin T2, shows differences in nuclear localization at distinct stages of adipogenesis. Overexpression of cdk9 increases the adipogenic potential of 3T3-L1 cells, whereas inhibition of cdk9 by specific cdk inhibitors, and dominant-negative cdk9 mutant impairs adipogenesis. We show that the positive effects of cdk9 on the differentiation of 3T3-L1 cells are mediated by a direct interaction with and phosphorylation of peroxisome proliferator-activated receptor gamma (PPARgamma), which is the master regulator of this process, on the promoter of PPARgamma target genes. PPARgamma-cdk9 interaction results in increased transcriptional activity of PPARgamma and therefore increased adipogenesis.

Original language	English
Journal	Molecular Endocrinology
Volume	20
Issue number	7
Pages (from-to)	1494-505
Number of pages	11
ISSN	0888-8809
DOIs	https://doi.org/10.1210/me.2005-0222
Publication status	Published - 2006

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Iankova, I., Petersen, R. K., Annicotte, J.-S., Chavey, C., Hansen, J. B., Kratchmarova, I., Sarruf, D., Benkirane, M., Kristiansen, K., & Fajas, L. (2006). Peroxisome proliferator-activated receptor gamma recruits the positive transcription elongation factor b complex to activate transcription and promote adipogenesis. Molecular Endocrinology, 20(7), 1494-505. https://doi.org/10.1210/me.2005-0222

Peroxisome proliferator-activated receptor gamma recruits the positive transcription elongation factor b complex to activate transcription and promote adipogenesis. / Iankova, Irena; Petersen, Rasmus K; Annicotte, Jean-Sébastien et al.
In: Molecular Endocrinology, Vol. 20, No. 7, 2006, p. 1494-505.

Research output: Contribution to journal › Journal article › Research › peer-review

Iankova, I, Petersen, RK, Annicotte, J-S, Chavey, C, Hansen, JB, Kratchmarova, I, Sarruf, D, Benkirane, M, Kristiansen, K & Fajas, L 2006, 'Peroxisome proliferator-activated receptor gamma recruits the positive transcription elongation factor b complex to activate transcription and promote adipogenesis.', Molecular Endocrinology, vol. 20, no. 7, pp. 1494-505. https://doi.org/10.1210/me.2005-0222

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title = "Peroxisome proliferator-activated receptor gamma recruits the positive transcription elongation factor b complex to activate transcription and promote adipogenesis.",

abstract = "Positive transcription elongation factor b (P-TEFb) phosphorylates the C-terminal domain of RNA polymerase II, facilitating transcriptional elongation. In addition to its participation in general transcription, P-TEFb is recruited to specific promoters by some transcription factors such as c-Myc or MyoD. The P-TEFb complex is composed of a cyclin-dependent kinase (cdk9) subunit and a regulatory partner (cyclin T1, cyclin T2, or cyclin K). Because cdk9 has been shown to participate in differentiation processes, such as muscle cell differentiation, we studied a possible role of cdk9 in adipogenesis. In this study we show that the expression of the cdk9 p55 isoform is highly regulated during 3T3-L1 adipocyte differentiation at RNA and protein levels. Furthermore, cdk9, as well as cyclin T1 and cyclin T2, shows differences in nuclear localization at distinct stages of adipogenesis. Overexpression of cdk9 increases the adipogenic potential of 3T3-L1 cells, whereas inhibition of cdk9 by specific cdk inhibitors, and dominant-negative cdk9 mutant impairs adipogenesis. We show that the positive effects of cdk9 on the differentiation of 3T3-L1 cells are mediated by a direct interaction with and phosphorylation of peroxisome proliferator-activated receptor gamma (PPARgamma), which is the master regulator of this process, on the promoter of PPARgamma target genes. PPARgamma-cdk9 interaction results in increased transcriptional activity of PPARgamma and therefore increased adipogenesis.",

author = "Irena Iankova and Petersen, {Rasmus K} and Jean-S{\'e}bastien Annicotte and Carine Chavey and Hansen, {Jacob B} and Irina Kratchmarova and David Sarruf and Monsef Benkirane and Karsten Kristiansen and Lluis Fajas",

note = "Keywords: 3T3 Cells; Adipogenesis; Animals; CHO Cells; Cell Differentiation; Cell Division; Cricetinae; Cyclin-Dependent Kinase 9; Dichlororibofuranosylbenzimidazole; Gene Expression Regulation; Mice; PPAR gamma; Phosphorylation; Positive Transcriptional Elongation Factor B; Protein Binding",

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doi = "10.1210/me.2005-0222",

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T1 - Peroxisome proliferator-activated receptor gamma recruits the positive transcription elongation factor b complex to activate transcription and promote adipogenesis.

AU - Iankova, Irena

AU - Petersen, Rasmus K

AU - Annicotte, Jean-Sébastien

AU - Chavey, Carine

AU - Hansen, Jacob B

AU - Kratchmarova, Irina

AU - Sarruf, David

AU - Benkirane, Monsef

AU - Kristiansen, Karsten

AU - Fajas, Lluis

N1 - Keywords: 3T3 Cells; Adipogenesis; Animals; CHO Cells; Cell Differentiation; Cell Division; Cricetinae; Cyclin-Dependent Kinase 9; Dichlororibofuranosylbenzimidazole; Gene Expression Regulation; Mice; PPAR gamma; Phosphorylation; Positive Transcriptional Elongation Factor B; Protein Binding

PY - 2006

Y1 - 2006

N2 - Positive transcription elongation factor b (P-TEFb) phosphorylates the C-terminal domain of RNA polymerase II, facilitating transcriptional elongation. In addition to its participation in general transcription, P-TEFb is recruited to specific promoters by some transcription factors such as c-Myc or MyoD. The P-TEFb complex is composed of a cyclin-dependent kinase (cdk9) subunit and a regulatory partner (cyclin T1, cyclin T2, or cyclin K). Because cdk9 has been shown to participate in differentiation processes, such as muscle cell differentiation, we studied a possible role of cdk9 in adipogenesis. In this study we show that the expression of the cdk9 p55 isoform is highly regulated during 3T3-L1 adipocyte differentiation at RNA and protein levels. Furthermore, cdk9, as well as cyclin T1 and cyclin T2, shows differences in nuclear localization at distinct stages of adipogenesis. Overexpression of cdk9 increases the adipogenic potential of 3T3-L1 cells, whereas inhibition of cdk9 by specific cdk inhibitors, and dominant-negative cdk9 mutant impairs adipogenesis. We show that the positive effects of cdk9 on the differentiation of 3T3-L1 cells are mediated by a direct interaction with and phosphorylation of peroxisome proliferator-activated receptor gamma (PPARgamma), which is the master regulator of this process, on the promoter of PPARgamma target genes. PPARgamma-cdk9 interaction results in increased transcriptional activity of PPARgamma and therefore increased adipogenesis.

AB - Positive transcription elongation factor b (P-TEFb) phosphorylates the C-terminal domain of RNA polymerase II, facilitating transcriptional elongation. In addition to its participation in general transcription, P-TEFb is recruited to specific promoters by some transcription factors such as c-Myc or MyoD. The P-TEFb complex is composed of a cyclin-dependent kinase (cdk9) subunit and a regulatory partner (cyclin T1, cyclin T2, or cyclin K). Because cdk9 has been shown to participate in differentiation processes, such as muscle cell differentiation, we studied a possible role of cdk9 in adipogenesis. In this study we show that the expression of the cdk9 p55 isoform is highly regulated during 3T3-L1 adipocyte differentiation at RNA and protein levels. Furthermore, cdk9, as well as cyclin T1 and cyclin T2, shows differences in nuclear localization at distinct stages of adipogenesis. Overexpression of cdk9 increases the adipogenic potential of 3T3-L1 cells, whereas inhibition of cdk9 by specific cdk inhibitors, and dominant-negative cdk9 mutant impairs adipogenesis. We show that the positive effects of cdk9 on the differentiation of 3T3-L1 cells are mediated by a direct interaction with and phosphorylation of peroxisome proliferator-activated receptor gamma (PPARgamma), which is the master regulator of this process, on the promoter of PPARgamma target genes. PPARgamma-cdk9 interaction results in increased transcriptional activity of PPARgamma and therefore increased adipogenesis.

U2 - 10.1210/me.2005-0222

DO - 10.1210/me.2005-0222

M3 - Journal article

C2 - 16484339

SN - 0888-8809

VL - 20

SP - 1494

EP - 1505

JO - Molecular Endocrinology

JF - Molecular Endocrinology

IS - 7

ER -

Peroxisome proliferator-activated receptor gamma recruits the positive transcription elongation factor b complex to activate transcription and promote adipogenesis.

Abstract

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