Abstract
The dynamic changes and structural patterns of DNA methylation of genes without CpG islands are poorly characterized. The relevance of CpG to the non-CpG methylation equilibrium in transcriptional repression is unknown. In this work, we analyzed the DNA methylation pattern of the 5́-flanking of the myogenin gene, a positive regulator of muscle differentiation with no CpG island and low CpG density, in both C2C12 muscle satellite cells and embryonic muscle. Embryonic brain was studied as a non-expressing tissue. High levels of both CpG and non-CpG methylation were observed in non-expressing experimental conditions. Both CpG and non-CpG methylation rapidly dropped during muscle differentiation and myogenin transcriptional activation, with an active demethylation dynamics. Non-CpG demethylation occurred more rapidly than CpG demethylation. Demethylation spread from initially highly methylated short CpC-rich elements to a virtually unmethylated status. These short elements have a high CpC content and density, share some motifs and largely coincide with putative recognition sequences of some differentiation-related transcription factors. Our findings point to a dynamically controlled equilibrium between CpG and non-CpG active demethylation in the transcriptional control of tissue-specific genes. The short CpC-rich elements are new structural features of the methylation machinery, whose functions may include priming the complete demethylation of a transcriptionally crucial DNA region.
| Original language | English |
|---|---|
| Pages (from-to) | 3965-3976 |
| Number of pages | 12 |
| Journal | Cell Cycle |
| Volume | 9 |
| Issue number | 19 |
| DOIs | |
| Publication status | Published - Oct 1 2010 |
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Keywords
- Active demethylation
- Demethylation dynamics
- Muscle differentiation
- Non-CpG island genes
- non-CpG methylation
- Short CpC-rich elements
- Transcriptional modulation
ASJC Scopus subject areas
- Cell Biology
- Molecular Biology
- Developmental Biology
Cite this
Early demethylation of non-CpG, CpC-rich, elements in the myogenin 5′-flanking region : A priming effect on the spreading of active demethylation? / Fuso, Andrea; Ferraguti, Giampiero; Grandoni, Francesco; Ruggeri, Raffaella; Scarpa, Sigfrido; Strom, Roberto; Lucarelli, Marco.
In: Cell Cycle, Vol. 9, No. 19, 01.10.2010, p. 3965-3976.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Early demethylation of non-CpG, CpC-rich, elements in the myogenin 5′-flanking region
T2 - A priming effect on the spreading of active demethylation?
AU - Fuso, Andrea
AU - Ferraguti, Giampiero
AU - Grandoni, Francesco
AU - Ruggeri, Raffaella
AU - Scarpa, Sigfrido
AU - Strom, Roberto
AU - Lucarelli, Marco
PY - 2010/10/1
Y1 - 2010/10/1
N2 - The dynamic changes and structural patterns of DNA methylation of genes without CpG islands are poorly characterized. The relevance of CpG to the non-CpG methylation equilibrium in transcriptional repression is unknown. In this work, we analyzed the DNA methylation pattern of the 5́-flanking of the myogenin gene, a positive regulator of muscle differentiation with no CpG island and low CpG density, in both C2C12 muscle satellite cells and embryonic muscle. Embryonic brain was studied as a non-expressing tissue. High levels of both CpG and non-CpG methylation were observed in non-expressing experimental conditions. Both CpG and non-CpG methylation rapidly dropped during muscle differentiation and myogenin transcriptional activation, with an active demethylation dynamics. Non-CpG demethylation occurred more rapidly than CpG demethylation. Demethylation spread from initially highly methylated short CpC-rich elements to a virtually unmethylated status. These short elements have a high CpC content and density, share some motifs and largely coincide with putative recognition sequences of some differentiation-related transcription factors. Our findings point to a dynamically controlled equilibrium between CpG and non-CpG active demethylation in the transcriptional control of tissue-specific genes. The short CpC-rich elements are new structural features of the methylation machinery, whose functions may include priming the complete demethylation of a transcriptionally crucial DNA region.
AB - The dynamic changes and structural patterns of DNA methylation of genes without CpG islands are poorly characterized. The relevance of CpG to the non-CpG methylation equilibrium in transcriptional repression is unknown. In this work, we analyzed the DNA methylation pattern of the 5́-flanking of the myogenin gene, a positive regulator of muscle differentiation with no CpG island and low CpG density, in both C2C12 muscle satellite cells and embryonic muscle. Embryonic brain was studied as a non-expressing tissue. High levels of both CpG and non-CpG methylation were observed in non-expressing experimental conditions. Both CpG and non-CpG methylation rapidly dropped during muscle differentiation and myogenin transcriptional activation, with an active demethylation dynamics. Non-CpG demethylation occurred more rapidly than CpG demethylation. Demethylation spread from initially highly methylated short CpC-rich elements to a virtually unmethylated status. These short elements have a high CpC content and density, share some motifs and largely coincide with putative recognition sequences of some differentiation-related transcription factors. Our findings point to a dynamically controlled equilibrium between CpG and non-CpG active demethylation in the transcriptional control of tissue-specific genes. The short CpC-rich elements are new structural features of the methylation machinery, whose functions may include priming the complete demethylation of a transcriptionally crucial DNA region.
KW - Active demethylation
KW - Demethylation dynamics
KW - Muscle differentiation
KW - Non-CpG island genes
KW - non-CpG methylation
KW - Short CpC-rich elements
KW - Transcriptional modulation
UR - http://www.scopus.com/inward/record.url?scp=77958482239&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77958482239&partnerID=8YFLogxK
U2 - 10.4161/cc.9.19.13193
DO - 10.4161/cc.9.19.13193
M3 - Article
VL - 9
SP - 3965
EP - 3976
JO - Cell Cycle
JF - Cell Cycle
SN - 1538-4101
IS - 19
ER -