Hdac3 Interaction with p300 Histone Acetyltransferase Regulates the Oligodendrocyte and Astrocyte Lineage Fate Switch

Liguo Zhang, Xuelian He, Lei Liu, Minqing Jiang, Chuntao Zhao, Haibo Wang, Danyang He, Tao Zheng, Xianyao Zhou, Aishlin Hassan, Zhixing Ma, Mei Xin, Zheng Sun, Mitchell A. Lazar, Steven A. Goldman, Eric N. Olson, Q. Richard Lu

Research output: Contribution to journalArticle

39 Scopus citations

Abstract

Establishment and maintenance of CNS glial cell identity ensures proper brain development and function, yet the epigenetic mechanisms underlying glial fate control remain poorly understood. Here, we show that the histone deacetylase Hdac3 controls oligodendrocyte-specification gene Olig2 expression and functions as a molecular switch for oligodendrocyte and astrocyte lineage determination. Hdac3 ablation leads to a significant increase of astrocytes with a concomitant loss of oligodendrocytes. Lineage tracing indicates that the ectopic astrocytes originate from oligodendrocyte progenitors. Genome-wide occupancy analysis reveals that Hdac3 interacts with p300 to activate oligodendroglial lineage-specific genes, while suppressing astroglial differentiation genes including NFIA. Furthermore, we find that Hdac3 modulates the acetylation state of Stat3 and competes with Stat3 for p300 binding to antagonize astrogliogenesis. Thus, our data suggest that Hdac3 cooperates with p300 to prime and maintain oligodendrocyte identity while inhibiting NFIA and Stat3-mediated astrogliogenesis, and thereby regulates phenotypic commitment at the point of oligodendrocyte-astrocytic fate decision.

Original languageEnglish (US)
Pages (from-to)316-330
Number of pages15
JournalDevelopmental Cell
Volume36
Issue number3
DOIs
StatePublished - Feb 8 2016

ASJC Scopus subject areas

  • Developmental Biology

Fingerprint Dive into the research topics of 'Hdac3 Interaction with p300 Histone Acetyltransferase Regulates the Oligodendrocyte and Astrocyte Lineage Fate Switch'. Together they form a unique fingerprint.

  • Cite this

    Zhang, L., He, X., Liu, L., Jiang, M., Zhao, C., Wang, H., He, D., Zheng, T., Zhou, X., Hassan, A., Ma, Z., Xin, M., Sun, Z., Lazar, M. A., Goldman, S. A., Olson, E. N., & Lu, Q. R. (2016). Hdac3 Interaction with p300 Histone Acetyltransferase Regulates the Oligodendrocyte and Astrocyte Lineage Fate Switch. Developmental Cell, 36(3), 316-330. https://doi.org/10.1016/j.devcel.2016.01.002