Histone deacetylase 3 prepares brown adipose tissue for acute thermogenic challenge

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

Standard

Histone deacetylase 3 prepares brown adipose tissue for acute thermogenic challenge. / Emmett, Matthew J.; Lim, Hee-Woong; Jager, Jennifer; Richter, Hannah J.; Adlanmerini, Marine; Peed, Lindsey C.; Briggs, Erika R.; Steger, David J.; Ma, Tao; Sims, Carrie A.; Baur, Joseph A.; Pei, Liming; Won, Kyoung-Jae; Seale, Patrick; Gerhart-Hines, Zachary; Lazar, Mitchell A.

In: Nature Genetics, Vol. 546, No. 7659, 2017, p. 544-448.

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

Harvard

Emmett, MJ, Lim, H-W, Jager, J, Richter, HJ, Adlanmerini, M, Peed, LC, Briggs, ER, Steger, DJ, Ma, T, Sims, CA, Baur, JA, Pei, L, Won, K-J, Seale, P, Gerhart-Hines, Z & Lazar, MA 2017, 'Histone deacetylase 3 prepares brown adipose tissue for acute thermogenic challenge', Nature Genetics, vol. 546, no. 7659, pp. 544-448. https://doi.org/10.1038/nature22819

APA

Emmett, M. J., Lim, H-W., Jager, J., Richter, H. J., Adlanmerini, M., Peed, L. C., Briggs, E. R., Steger, D. J., Ma, T., Sims, C. A., Baur, J. A., Pei, L., Won, K-J., Seale, P., Gerhart-Hines, Z., & Lazar, M. A. (2017). Histone deacetylase 3 prepares brown adipose tissue for acute thermogenic challenge. Nature Genetics, 546(7659), 544-448. https://doi.org/10.1038/nature22819

Vancouver

Emmett MJ, Lim H-W, Jager J, Richter HJ, Adlanmerini M, Peed LC et al. Histone deacetylase 3 prepares brown adipose tissue for acute thermogenic challenge. Nature Genetics. 2017;546(7659):544-448. https://doi.org/10.1038/nature22819

Author

Emmett, Matthew J. ; Lim, Hee-Woong ; Jager, Jennifer ; Richter, Hannah J. ; Adlanmerini, Marine ; Peed, Lindsey C. ; Briggs, Erika R. ; Steger, David J. ; Ma, Tao ; Sims, Carrie A. ; Baur, Joseph A. ; Pei, Liming ; Won, Kyoung-Jae ; Seale, Patrick ; Gerhart-Hines, Zachary ; Lazar, Mitchell A. / Histone deacetylase 3 prepares brown adipose tissue for acute thermogenic challenge. In: Nature Genetics. 2017 ; Vol. 546, No. 7659. pp. 544-448.

Bibtex

@article{2da57f3375894ab289b946a8c94ea03a,
title = "Histone deacetylase 3 prepares brown adipose tissue for acute thermogenic challenge",
abstract = "Brown adipose tissue is a thermogenic organ that dissipates chemical energy as heat to protect animals against hypothermia and to counteract metabolic disease1. However, the transcriptional mechanisms that determine the thermogenic capacity of brown adipose tissue before environmental cold are unknown. Here we show that histone deacetylase 3 (HDAC3) is required to activate brown adipose tissue enhancers to ensure thermogenic aptitude. Mice with brown adipose tissue-specific genetic ablation of HDAC3 become severely hypothermic and succumb to acute cold exposure. Uncoupling protein 1 (UCP1) is nearly absent in brown adipose tissue lacking HDAC3, and there is also marked downregulation of mitochondrial oxidative phosphorylation genes resulting in diminished mitochondrial respiration. Remarkably, although HDAC3 acts canonically as a transcriptional corepressor2, it functions as a coactivator of oestrogen-related receptor α (ERRα) in brown adipose tissue. HDAC3 coactivation of ERRα is mediated by deacetylation of PGC-1α and is required for the transcription of Ucp1, Ppargc1a (encoding PGC-1α), and oxidative phosphorylation genes. Importantly, HDAC3 promotes the basal transcription of these genes independently of adrenergic stimulation. Thus, HDAC3 uniquely primes Ucp1 and the thermogenic transcriptional program to maintain a critical capacity for thermogenesis in brown adipose tissue that can be rapidly engaged upon exposure to dangerously cold temperature.",
author = "Emmett, {Matthew J.} and Hee-Woong Lim and Jennifer Jager and Richter, {Hannah J.} and Marine Adlanmerini and Peed, {Lindsey C.} and Briggs, {Erika R.} and Steger, {David J.} and Tao Ma and Sims, {Carrie A.} and Baur, {Joseph A.} and Liming Pei and Kyoung-Jae Won and Patrick Seale and Zachary Gerhart-Hines and Lazar, {Mitchell A.}",
year = "2017",
doi = "10.1038/nature22819",
language = "English",
volume = "546",
pages = "544--448",
journal = "Nature Genetics",
issn = "1061-4036",
publisher = "nature publishing group",
number = "7659",

}

RIS

TY - JOUR

T1 - Histone deacetylase 3 prepares brown adipose tissue for acute thermogenic challenge

AU - Emmett, Matthew J.

AU - Lim, Hee-Woong

AU - Jager, Jennifer

AU - Richter, Hannah J.

AU - Adlanmerini, Marine

AU - Peed, Lindsey C.

AU - Briggs, Erika R.

AU - Steger, David J.

AU - Ma, Tao

AU - Sims, Carrie A.

AU - Baur, Joseph A.

AU - Pei, Liming

AU - Won, Kyoung-Jae

AU - Seale, Patrick

AU - Gerhart-Hines, Zachary

AU - Lazar, Mitchell A.

PY - 2017

Y1 - 2017

N2 - Brown adipose tissue is a thermogenic organ that dissipates chemical energy as heat to protect animals against hypothermia and to counteract metabolic disease1. However, the transcriptional mechanisms that determine the thermogenic capacity of brown adipose tissue before environmental cold are unknown. Here we show that histone deacetylase 3 (HDAC3) is required to activate brown adipose tissue enhancers to ensure thermogenic aptitude. Mice with brown adipose tissue-specific genetic ablation of HDAC3 become severely hypothermic and succumb to acute cold exposure. Uncoupling protein 1 (UCP1) is nearly absent in brown adipose tissue lacking HDAC3, and there is also marked downregulation of mitochondrial oxidative phosphorylation genes resulting in diminished mitochondrial respiration. Remarkably, although HDAC3 acts canonically as a transcriptional corepressor2, it functions as a coactivator of oestrogen-related receptor α (ERRα) in brown adipose tissue. HDAC3 coactivation of ERRα is mediated by deacetylation of PGC-1α and is required for the transcription of Ucp1, Ppargc1a (encoding PGC-1α), and oxidative phosphorylation genes. Importantly, HDAC3 promotes the basal transcription of these genes independently of adrenergic stimulation. Thus, HDAC3 uniquely primes Ucp1 and the thermogenic transcriptional program to maintain a critical capacity for thermogenesis in brown adipose tissue that can be rapidly engaged upon exposure to dangerously cold temperature.

AB - Brown adipose tissue is a thermogenic organ that dissipates chemical energy as heat to protect animals against hypothermia and to counteract metabolic disease1. However, the transcriptional mechanisms that determine the thermogenic capacity of brown adipose tissue before environmental cold are unknown. Here we show that histone deacetylase 3 (HDAC3) is required to activate brown adipose tissue enhancers to ensure thermogenic aptitude. Mice with brown adipose tissue-specific genetic ablation of HDAC3 become severely hypothermic and succumb to acute cold exposure. Uncoupling protein 1 (UCP1) is nearly absent in brown adipose tissue lacking HDAC3, and there is also marked downregulation of mitochondrial oxidative phosphorylation genes resulting in diminished mitochondrial respiration. Remarkably, although HDAC3 acts canonically as a transcriptional corepressor2, it functions as a coactivator of oestrogen-related receptor α (ERRα) in brown adipose tissue. HDAC3 coactivation of ERRα is mediated by deacetylation of PGC-1α and is required for the transcription of Ucp1, Ppargc1a (encoding PGC-1α), and oxidative phosphorylation genes. Importantly, HDAC3 promotes the basal transcription of these genes independently of adrenergic stimulation. Thus, HDAC3 uniquely primes Ucp1 and the thermogenic transcriptional program to maintain a critical capacity for thermogenesis in brown adipose tissue that can be rapidly engaged upon exposure to dangerously cold temperature.

U2 - 10.1038/nature22819

DO - 10.1038/nature22819

M3 - Journal article

C2 - 28614293

VL - 546

SP - 544

EP - 448

JO - Nature Genetics

JF - Nature Genetics

SN - 1061-4036

IS - 7659

ER -

ID: 182539799