ETO/MTG8 is an inhibitor of C/EBP beta activity and a regulator of early adipogenesis

JJ Rochford; RK Semple; M Laudes; KB Boyle; C Christodoulides; C Mulligan; CJ Lelliott; S Schinner; D Hadaschik; M Mahadevan; JK Sethi; A Vidal-Puig; S O'Rahilly

doi:10.1128/MCB.24.22.9863-9872.2004

ETO/MTG8 is an inhibitor of C/EBP beta activity and a regulator of early adipogenesis

JJ Rochford, RK Semple, M Laudes, KB Boyle, C Christodoulides, C Mulligan, CJ Lelliott, S Schinner, D Hadaschik, M Mahadevan, JK Sethi, A Vidal-Puig, S O'Rahilly^*

^*Corresponding author for this work

The Rowett Institute of Nutrition and Health

Research output: Contribution to journal › Article › peer-review

71 Citations (Scopus)

Abstract

The putative transcriptional corepressor ETO/MTG8 has been extensively studied due to its involvement in a chromosomal translocation causing the t(8;21) form of acute myeloid leukemia. Despite this, the role of ETO in normal physiology has remained obscure. Here we show that ETO is highly expressed in preadipocytes and acts as an inhibitor of C/EBPbeta during early adipogenesis, contributing to its characteristically delayed activation. ETO prevents both the transcriptional activation of the C/EBPalpha promoter by C/EBPbeta and its concurrent accumulation in centromeric sites during early adipogenesis. ETO expression rapidly reduces after the initiation of adipogenesis, and this is essential to the normal induction of adipogenic gene expression. These findings define, for the first time, a molecular role for ETO in normal physiology as an inhibitor of C/EBPbeta and a novel regulator of early adipogenesis.

Original language	English
Pages (from-to)	9863-9872
Number of pages	10
Journal	Molecular and Cellular Biology
Volume	24
Issue number	22
DOIs	https://doi.org/10.1128/MCB.24.22.9863-9872.2004
Publication status	Published - Nov 2004

Keywords

CCAAT/ENHANCER-BINDING PROTEINS
RECEPTOR GAMMA-2 PROMOTER
ADIPOCYTE DIFFERENTIATION
3T3-L1 PREADIPOCYTES
INSULIN SENSITIVITY
FUSION PROTEIN
GENE PROMOTER
GROWTH-FACTOR
MICE LACKING
ALPHA-GENE

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Rochford, JJ., Semple, RK., Laudes, M., Boyle, KB., Christodoulides, C., Mulligan, C., Lelliott, CJ., Schinner, S., Hadaschik, D., Mahadevan, M., Sethi, JK., Vidal-Puig, A., & O'Rahilly, S. (2004). ETO/MTG8 is an inhibitor of C/EBP beta activity and a regulator of early adipogenesis. Molecular and Cellular Biology, 24(22), 9863-9872. https://doi.org/10.1128/MCB.24.22.9863-9872.2004

Rochford, JJ, Semple, RK, Laudes, M, Boyle, KB, Christodoulides, C, Mulligan, C, Lelliott, CJ, Schinner, S, Hadaschik, D, Mahadevan, M, Sethi, JK, Vidal-Puig, A & O'Rahilly, S 2004, 'ETO/MTG8 is an inhibitor of C/EBP beta activity and a regulator of early adipogenesis', Molecular and Cellular Biology, vol. 24, no. 22, pp. 9863-9872. https://doi.org/10.1128/MCB.24.22.9863-9872.2004

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title = "ETO/MTG8 is an inhibitor of C/EBP beta activity and a regulator of early adipogenesis",

abstract = "The putative transcriptional corepressor ETO/MTG8 has been extensively studied due to its involvement in a chromosomal translocation causing the t(8;21) form of acute myeloid leukemia. Despite this, the role of ETO in normal physiology has remained obscure. Here we show that ETO is highly expressed in preadipocytes and acts as an inhibitor of C/EBPbeta during early adipogenesis, contributing to its characteristically delayed activation. ETO prevents both the transcriptional activation of the C/EBPalpha promoter by C/EBPbeta and its concurrent accumulation in centromeric sites during early adipogenesis. ETO expression rapidly reduces after the initiation of adipogenesis, and this is essential to the normal induction of adipogenic gene expression. These findings define, for the first time, a molecular role for ETO in normal physiology as an inhibitor of C/EBPbeta and a novel regulator of early adipogenesis.",

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author = "JJ Rochford and RK Semple and M Laudes and KB Boyle and C Christodoulides and C Mulligan and CJ Lelliott and S Schinner and D Hadaschik and M Mahadevan and JK Sethi and A Vidal-Puig and S O'Rahilly",

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AU - Rochford, JJ

AU - Semple, RK

AU - Laudes, M

AU - Boyle, KB

AU - Christodoulides, C

AU - Mulligan, C

AU - Lelliott, CJ

AU - Schinner, S

AU - Hadaschik, D

AU - Mahadevan, M

AU - Sethi, JK

AU - Vidal-Puig, A

AU - O'Rahilly, S

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N2 - The putative transcriptional corepressor ETO/MTG8 has been extensively studied due to its involvement in a chromosomal translocation causing the t(8;21) form of acute myeloid leukemia. Despite this, the role of ETO in normal physiology has remained obscure. Here we show that ETO is highly expressed in preadipocytes and acts as an inhibitor of C/EBPbeta during early adipogenesis, contributing to its characteristically delayed activation. ETO prevents both the transcriptional activation of the C/EBPalpha promoter by C/EBPbeta and its concurrent accumulation in centromeric sites during early adipogenesis. ETO expression rapidly reduces after the initiation of adipogenesis, and this is essential to the normal induction of adipogenic gene expression. These findings define, for the first time, a molecular role for ETO in normal physiology as an inhibitor of C/EBPbeta and a novel regulator of early adipogenesis.

AB - The putative transcriptional corepressor ETO/MTG8 has been extensively studied due to its involvement in a chromosomal translocation causing the t(8;21) form of acute myeloid leukemia. Despite this, the role of ETO in normal physiology has remained obscure. Here we show that ETO is highly expressed in preadipocytes and acts as an inhibitor of C/EBPbeta during early adipogenesis, contributing to its characteristically delayed activation. ETO prevents both the transcriptional activation of the C/EBPalpha promoter by C/EBPbeta and its concurrent accumulation in centromeric sites during early adipogenesis. ETO expression rapidly reduces after the initiation of adipogenesis, and this is essential to the normal induction of adipogenic gene expression. These findings define, for the first time, a molecular role for ETO in normal physiology as an inhibitor of C/EBPbeta and a novel regulator of early adipogenesis.

KW - CCAAT/ENHANCER-BINDING PROTEINS

KW - RECEPTOR GAMMA-2 PROMOTER

KW - ADIPOCYTE DIFFERENTIATION

KW - 3T3-L1 PREADIPOCYTES

KW - INSULIN SENSITIVITY

KW - FUSION PROTEIN

KW - GENE PROMOTER

KW - GROWTH-FACTOR

KW - MICE LACKING

KW - ALPHA-GENE

U2 - 10.1128/MCB.24.22.9863-9872.2004

DO - 10.1128/MCB.24.22.9863-9872.2004

M3 - Article

SN - 0270-7306

VL - 24

SP - 9863

EP - 9872

JO - Molecular and Cellular Biology

JF - Molecular and Cellular Biology

IS - 22

ER -

ETO/MTG8 is an inhibitor of C/EBP beta activity and a regulator of early adipogenesis

Abstract

Keywords

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