H4R3 methylation facilitates β-globin transcription by regulating histone acetyltransferase binding and H3 acetylation

Xingguo Li, Xin Hu, Bhavita Patel, Zhuo Zhou, Shermi Liang, River Ybarra, Yi Qiu, Gary Felsenfeld, Jörg Bungert, Suming Huang

Research output: Contribution to journalArticlepeer-review

62 Scopus citations

Abstract

Histone modifications play an important role in the process of transcription. However, in contrast to lysine methylation, the role of arginine methylation in chromatin structure and transcription has been underexplored. The globin genes are regulated by a highly organized chromatin structure that juxtaposes the locus control region (LCR) with downstream globin genes. We report here that the targeted recruitment of asymmetric dimethyl H4R3 catalyzed by PRMT1 (protein arginine methyltransferase 1) facilitates histone H3 acetylation on Lys9/Lys14. Dimethyl H4R3 provides a binding surface for P300/CBP-associated factor (PCAF) and directly enhances histone H3 acetylation in vitro.We show that these active modifications are essential for efficient interactions between the LCR and the βmaj-promoter as well as transcription of the β-globin gene. Furthermore, knockdown (KD) of PRMT1 by RNA interference in erythroid progenitor cells prevents histone acetylation, enhancer and promoter interaction, and recruitment of transcription complexes to the active β-globin promoter. Reintroducing rat PRMT1 into the PRMT1 KD MEL cells rescues PRMT1 binding, β-globin transcription, and erythroid differentiation. Taken together, our data suggest that PRMT1-mediated dimethyl H4R3 facilitates histone acetylation and enhancer/promoter communications, which lead to the efficient recruitment of transcription preinitiation complexes to active promoters.

Original languageEnglish (US)
Pages (from-to)2028-2037
Number of pages10
JournalBlood
Volume115
Issue number10
DOIs
StatePublished - Mar 11 2010

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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