PGC-1 coactivator activity is required for murine erythropoiesis

Shuaiying Cui, Osamu Tanabe, Kim Chew Lim, H. Eric Xu, X. Edward Zhou, Jiandie D. Lin, Lihong Shi, Lindsay Schmidt, Andrew Campbell, Ritsuko Shimizu, Masayuki Yamamoto, James Douglas Engel

Research output: Contribution to journalArticlepeer-review

16 Citations (Scopus)

Abstract

Peroxisome proliferator-activated receptor gamma (PPARγ) coactivator 1α (PGC-1α) and PGC-1β have been shown to be intimately involved in the transcriptional regulation of cellular energy metabolism as well as other biological processes, but both coactivator proteins are expressed in many other tissues and organs in which their function is, in essence, unexplored. Here, we found that both PGC-1 proteins are abundantly expressed in maturing erythroid cells. PGC-1α and PGC-1β compound null mutant (Pgc-1c) animals express less β-like globin mRNAs throughout development; consequently, neonatal Pgc-1c mice exhibit growth retardation and profound anemia. Flow cytometry shows that the number of mature erythrocytes is markedly reduced in neonatal Pgc-1c pups, indicating that erythropoiesis is severely compromised. Furthermore, hematoxylin and eosin staining revealed necrotic cell death and cell loss in Pgc-1c livers and spleen. Chromatin immunoprecipitation studies revealed that both PGC-1α and -1β, as well as two nuclear receptors, TR2 and TR4, coordinately bind to the various globin gene promoters. In addition, PGC-1α and -1β can interact with TR4 to potentiate transcriptional activation. These data provide new insights into our understanding of globin gene regulation and raise the interesting possibility that the PGC-1 coactivators can interact with TR4 to elicit differential stage-specific effects on globin gene transcription.

Original languageEnglish
Pages (from-to)1956-1965
Number of pages10
JournalMolecular and cellular biology
Volume34
Issue number11
DOIs
Publication statusPublished - 2014 Jun

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'PGC-1 coactivator activity is required for murine erythropoiesis'. Together they form a unique fingerprint.

Cite this