Chromatin accessibility at a STAT3 target site is altered prior to astrocyte differentiation

Satoshi Urayama, Katsunori Semi, Tsukasa Sanosaka, Yukina Hori, Masakazu Namihira, Jun Kohyama, Takumi Takizawa, Kinichi Nakashima

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

DNA demethylation of astrocyte-specific gene promoters and STAT3 activation in neural precursor cells (NPCs) are essential for astrogliogenesis in the developing brain. To date, it remains unclear whether DNA methylation is the sole epigenetic determinant responsible for suppressing astrocyte-specific genes. Here, we used mouse embryonic stem cells (TKO ESCs) that lacked all 3 DNA methyltransferase genes, Dnmt1, Dnmt3a, and Dnmt3b, and thereby exhibit complete demethylation of the astrocyte-specific glial fibrillary acidic protein (Gfap) gene promoter. We found that although the Gfap promoter was demethylated, STAT3 failed to bind to its cognate element to induce Gfap transcription, whereas it induced transcription of a different target gene, Socs3. Moreover, although the Gfap promoter region containing the STAT3-binding site (GSBS) is enriched with transcription-repressive histone modifications, such as methylation of H3 at lysine 9 (H3K9me3) and H3K27me3, the reduction of these modifications in TKO ESCs was not sufficient for binding of STAT3 at GSBS. Furthermore, GSBS was digested by micrococcal nuclease in late-gestational NPCs that express GFAP upon LIF stimulation, but not in cells that show no expression of GFAP even in the presence of LIF, indicating that STAT3 can access GSBS in the former cells. We further showed that expression of NF-1A, which is known to potentiate differentiation of mid-gestational NPCs into astrocytes, increased its accessibility. Taken together, our results suggest that chromatin accessibility of GSBS plays a critical role in the regulation of Gfap expression.

Original languageEnglish
Pages (from-to)55-66
Number of pages12
JournalCell structure and function
Volume38
Issue number1
DOIs
Publication statusPublished - Apr 26 2013
Externally publishedYes

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Glial Fibrillary Acidic Protein
Astrocytes
Chromatin
Genes
Histone Code
Micrococcal Nuclease
DNA
Methyltransferases
DNA Methylation
Genetic Promoter Regions
Epigenomics
Methylation
Lysine
Binding Sites
Brain

All Science Journal Classification (ASJC) codes

  • Physiology
  • Molecular Biology
  • Cell Biology

Cite this

Chromatin accessibility at a STAT3 target site is altered prior to astrocyte differentiation. / Urayama, Satoshi; Semi, Katsunori; Sanosaka, Tsukasa; Hori, Yukina; Namihira, Masakazu; Kohyama, Jun; Takizawa, Takumi; Nakashima, Kinichi.

In: Cell structure and function, Vol. 38, No. 1, 26.04.2013, p. 55-66.

Research output: Contribution to journalArticle

Urayama, S, Semi, K, Sanosaka, T, Hori, Y, Namihira, M, Kohyama, J, Takizawa, T & Nakashima, K 2013, 'Chromatin accessibility at a STAT3 target site is altered prior to astrocyte differentiation', Cell structure and function, vol. 38, no. 1, pp. 55-66. https://doi.org/10.1247/csf.12034
Urayama, Satoshi ; Semi, Katsunori ; Sanosaka, Tsukasa ; Hori, Yukina ; Namihira, Masakazu ; Kohyama, Jun ; Takizawa, Takumi ; Nakashima, Kinichi. / Chromatin accessibility at a STAT3 target site is altered prior to astrocyte differentiation. In: Cell structure and function. 2013 ; Vol. 38, No. 1. pp. 55-66.
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