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ZFIN ID: ZDB-PUB-180223-19
Ezh2 promotes clock function and hematopoiesis independent of histone methyltransferase activity in zebrafish
Zhong, Y., Ye, Q., Chen, C., Wang, M., Wang, H.
Date: 2018
Source: Nucleic acids research   46(7): 3382-3399 (Journal)
Registered Authors: Wang, Han, Wang, Mingyong, Ye, Qiang, Zhong, Yingbin
Keywords: none
Microarrays: GEO:GSE103913
MeSH Terms:
  • Animals
  • Circadian Clocks/genetics*
  • Circadian Rhythm Signaling Peptides and Proteins/genetics*
  • E-Box Elements/genetics
  • Enhancer of Zeste Homolog 2 Protein/genetics*
  • Gene Expression Regulation, Developmental/genetics
  • Hematopoiesis/genetics*
  • Humans
  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck)/genetics
  • Period Circadian Proteins/genetics
  • Polycomb Repressive Complex 2/genetics
  • Zebrafish/genetics
  • Zebrafish/growth & development
  • Zebrafish Proteins/genetics
PubMed: 29447387 Full text @ Nucleic Acids Res.
EZH2 is a subunit of polycomb repressive complex 2 (PRC2) that silences gene transcription via H3K27me3 and was shown to be essential for mammalian liver circadian regulation and hematopoiesis through gene silencing. Much less, however, is known about how Ezh2 acts in live zebrafish. Here, we show that zebrafish ezh2 is regulated directly by the circadian clock via both E-box and RORE motif, while core circadian clock genes per1a, per1b, cry1aa and cry1ab are down-regulated in ezh2 null mutant and ezh2 morphant zebrafish, and either knockdown or overexpression of ezh2 alters locomotor rhythms, indicating that Ezh2 is required for zebrafish circadian regulation. In contrast to its canonical silencing function, zebrafish Ezh2 up-regulates these key circadian clock genes independent of histone methyltransferase activity by directly binding to key circadian clock proteins. Similarly, Ezh2 contributes to hematopoiesis by enhancing expression of hematopoietic genes such as cmyb and lck. Together, our findings demonstrate for the first time that Ezh2 acts in both circadian regulation and hematopoiesis independent of silencing PRC2.