Promyelocytic leukemia protein in retinoic acid-induced chromatin remodeling of Oct4 gene promoter

Ya Shan Chuang, Wei Hong Huang, Sung Wook Park, Shawna D. Persaud, Chen Hsiang Hung, Ping Chih Ho, Li-Na Wei

Research output: Contribution to journalArticlepeer-review

42 Scopus citations


Promyelocytic leukemia (Pml) protein is required for Oct4 gene expression and the maintenance of its open chromatin conformation in stem cells. In proliferating stem cells, Pml-nuclear body, along with transcription factors TR2, steroidogenic factor 1 (SF1) and Sp1, and Brg1-dependent chromatin remodeling complex (BRGC), associates with conserved region 1 (CR1) of this promoter to maintain a nucleosome-free region for gene activity. Retinoic acid (RA) rapidly downregulates Pml, resulting in the replacement of BRGC with Brm-containing remodeling complex, disassociation of SF1 and Sp1, retaining of TR2, recruitment of receptor-interaction protein 140, G9a and HP1c, and sequential insertion of two nucleosomes on CR1 that progressively displays repressive heterochromatin marks. This study demonstrates a functional role for Pml in maintaining a specific open chromatin conformation of the Oct4 promoter region for its constant expression in stem cells; and illustrates the mechanism underlying RA-induced chromatin remodeling of Oct4 gene in differentiating cells, in which Pml plays a critical role. The study also demonstrates a novel mode of chromatin remodeling, which occurs by repositioning and sequentially inserting nucleosomes into a specific region of the gene promoter to compact the chromatin in differentiating cells.

Original languageEnglish (US)
Pages (from-to)660-669
Number of pages10
Issue number4
StatePublished - Apr 2011


  • Chromatin remodeling
  • Embryonic stem cells
  • Oct4
  • P19
  • Pml-NB
  • Retinoic acid
  • TR2


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