HDAC1 and HDAC2 regulate oligodendrocyte differentiation by disrupting the Β-catenin-TCF interaction

Feng Ye, Ying Chen, Thaonguyen Hoang, Rusty L. Montgomery, Xian Hui Zhao, Hong Bu, Tom Hu, Makoto M. Taketo, Johan H. Van Es, Hans Clevers, Jenny Hsieh, Rhonda S Bassel-Duby, Eric N Olson, Q. Richard Lu

Research output: Contribution to journalArticle

353 Citations (Scopus)

Abstract

Oligodendrocyte development is regulated by the interaction of repressors and activators in a complex transcriptional network. We found that two histone-modifying enzymes, HDAC1 and HDAC2, were required for oligodendrocyte formation. Genetic deletion of both Hdac1 and Hdac2 in oligodendrocyte lineage cells resulted in stabilization and nuclear translocation of Β-catenin, which negatively regulates oligodendrocyte development by repressing Olig2 expression. We further identified the oligodendrocyte-restricted transcription factor TCF7L2/TCF4 as a bipartite co-effector of Β-catenin for regulating oligodendrocyte differentiation. Targeted disruption of Tcf7l2 in mice led to severe defects in oligodendrocyte maturation, whereas expression of its dominant-repressive form promoted precocious oligodendrocyte specification in developing chick neural tube. Transcriptional co-repressors HDAC1 and HDAC2 compete with Β-catenin for TCF7L2 interaction to regulate downstream genes involved in oligodendrocyte differentiation. Thus, crosstalk between HDAC1/2 and the canonical Wnt signaling pathway mediated by TCF7L2 serves as a regulatory mechanism for oligodendrocyte differentiation.

Original languageEnglish (US)
Pages (from-to)829-838
Number of pages10
JournalNature Neuroscience
Volume12
Issue number7
DOIs
StatePublished - Jul 2009

Fingerprint

Catenins
Oligodendroglia
Wnt Signaling Pathway
Transcription Factor 7-Like 2 Protein
Co-Repressor Proteins
Neural Tube
Gene Regulatory Networks
Histones

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Ye, F., Chen, Y., Hoang, T., Montgomery, R. L., Zhao, X. H., Bu, H., ... Lu, Q. R. (2009). HDAC1 and HDAC2 regulate oligodendrocyte differentiation by disrupting the Β-catenin-TCF interaction. Nature Neuroscience, 12(7), 829-838. https://doi.org/10.1038/nn.2333

HDAC1 and HDAC2 regulate oligodendrocyte differentiation by disrupting the Β-catenin-TCF interaction. / Ye, Feng; Chen, Ying; Hoang, Thaonguyen; Montgomery, Rusty L.; Zhao, Xian Hui; Bu, Hong; Hu, Tom; Taketo, Makoto M.; Van Es, Johan H.; Clevers, Hans; Hsieh, Jenny; Bassel-Duby, Rhonda S; Olson, Eric N; Lu, Q. Richard.

In: Nature Neuroscience, Vol. 12, No. 7, 07.2009, p. 829-838.

Research output: Contribution to journalArticle

Ye, F, Chen, Y, Hoang, T, Montgomery, RL, Zhao, XH, Bu, H, Hu, T, Taketo, MM, Van Es, JH, Clevers, H, Hsieh, J, Bassel-Duby, RS, Olson, EN & Lu, QR 2009, 'HDAC1 and HDAC2 regulate oligodendrocyte differentiation by disrupting the Β-catenin-TCF interaction', Nature Neuroscience, vol. 12, no. 7, pp. 829-838. https://doi.org/10.1038/nn.2333
Ye, Feng ; Chen, Ying ; Hoang, Thaonguyen ; Montgomery, Rusty L. ; Zhao, Xian Hui ; Bu, Hong ; Hu, Tom ; Taketo, Makoto M. ; Van Es, Johan H. ; Clevers, Hans ; Hsieh, Jenny ; Bassel-Duby, Rhonda S ; Olson, Eric N ; Lu, Q. Richard. / HDAC1 and HDAC2 regulate oligodendrocyte differentiation by disrupting the Β-catenin-TCF interaction. In: Nature Neuroscience. 2009 ; Vol. 12, No. 7. pp. 829-838.
@article{093bce9243a748c08cd975fad15c587d,
title = "HDAC1 and HDAC2 regulate oligodendrocyte differentiation by disrupting the Β-catenin-TCF interaction",
abstract = "Oligodendrocyte development is regulated by the interaction of repressors and activators in a complex transcriptional network. We found that two histone-modifying enzymes, HDAC1 and HDAC2, were required for oligodendrocyte formation. Genetic deletion of both Hdac1 and Hdac2 in oligodendrocyte lineage cells resulted in stabilization and nuclear translocation of Β-catenin, which negatively regulates oligodendrocyte development by repressing Olig2 expression. We further identified the oligodendrocyte-restricted transcription factor TCF7L2/TCF4 as a bipartite co-effector of Β-catenin for regulating oligodendrocyte differentiation. Targeted disruption of Tcf7l2 in mice led to severe defects in oligodendrocyte maturation, whereas expression of its dominant-repressive form promoted precocious oligodendrocyte specification in developing chick neural tube. Transcriptional co-repressors HDAC1 and HDAC2 compete with Β-catenin for TCF7L2 interaction to regulate downstream genes involved in oligodendrocyte differentiation. Thus, crosstalk between HDAC1/2 and the canonical Wnt signaling pathway mediated by TCF7L2 serves as a regulatory mechanism for oligodendrocyte differentiation.",
author = "Feng Ye and Ying Chen and Thaonguyen Hoang and Montgomery, {Rusty L.} and Zhao, {Xian Hui} and Hong Bu and Tom Hu and Taketo, {Makoto M.} and {Van Es}, {Johan H.} and Hans Clevers and Jenny Hsieh and Bassel-Duby, {Rhonda S} and Olson, {Eric N} and Lu, {Q. Richard}",
year = "2009",
month = "7",
doi = "10.1038/nn.2333",
language = "English (US)",
volume = "12",
pages = "829--838",
journal = "Nature Neuroscience",
issn = "1097-6256",
publisher = "Nature Publishing Group",
number = "7",

}

TY - JOUR

T1 - HDAC1 and HDAC2 regulate oligodendrocyte differentiation by disrupting the Β-catenin-TCF interaction

AU - Ye, Feng

AU - Chen, Ying

AU - Hoang, Thaonguyen

AU - Montgomery, Rusty L.

AU - Zhao, Xian Hui

AU - Bu, Hong

AU - Hu, Tom

AU - Taketo, Makoto M.

AU - Van Es, Johan H.

AU - Clevers, Hans

AU - Hsieh, Jenny

AU - Bassel-Duby, Rhonda S

AU - Olson, Eric N

AU - Lu, Q. Richard

PY - 2009/7

Y1 - 2009/7

N2 - Oligodendrocyte development is regulated by the interaction of repressors and activators in a complex transcriptional network. We found that two histone-modifying enzymes, HDAC1 and HDAC2, were required for oligodendrocyte formation. Genetic deletion of both Hdac1 and Hdac2 in oligodendrocyte lineage cells resulted in stabilization and nuclear translocation of Β-catenin, which negatively regulates oligodendrocyte development by repressing Olig2 expression. We further identified the oligodendrocyte-restricted transcription factor TCF7L2/TCF4 as a bipartite co-effector of Β-catenin for regulating oligodendrocyte differentiation. Targeted disruption of Tcf7l2 in mice led to severe defects in oligodendrocyte maturation, whereas expression of its dominant-repressive form promoted precocious oligodendrocyte specification in developing chick neural tube. Transcriptional co-repressors HDAC1 and HDAC2 compete with Β-catenin for TCF7L2 interaction to regulate downstream genes involved in oligodendrocyte differentiation. Thus, crosstalk between HDAC1/2 and the canonical Wnt signaling pathway mediated by TCF7L2 serves as a regulatory mechanism for oligodendrocyte differentiation.

AB - Oligodendrocyte development is regulated by the interaction of repressors and activators in a complex transcriptional network. We found that two histone-modifying enzymes, HDAC1 and HDAC2, were required for oligodendrocyte formation. Genetic deletion of both Hdac1 and Hdac2 in oligodendrocyte lineage cells resulted in stabilization and nuclear translocation of Β-catenin, which negatively regulates oligodendrocyte development by repressing Olig2 expression. We further identified the oligodendrocyte-restricted transcription factor TCF7L2/TCF4 as a bipartite co-effector of Β-catenin for regulating oligodendrocyte differentiation. Targeted disruption of Tcf7l2 in mice led to severe defects in oligodendrocyte maturation, whereas expression of its dominant-repressive form promoted precocious oligodendrocyte specification in developing chick neural tube. Transcriptional co-repressors HDAC1 and HDAC2 compete with Β-catenin for TCF7L2 interaction to regulate downstream genes involved in oligodendrocyte differentiation. Thus, crosstalk between HDAC1/2 and the canonical Wnt signaling pathway mediated by TCF7L2 serves as a regulatory mechanism for oligodendrocyte differentiation.

UR - http://www.scopus.com/inward/record.url?scp=67649797866&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=67649797866&partnerID=8YFLogxK

U2 - 10.1038/nn.2333

DO - 10.1038/nn.2333

M3 - Article

VL - 12

SP - 829

EP - 838

JO - Nature Neuroscience

JF - Nature Neuroscience

SN - 1097-6256

IS - 7

ER -