| Interplay between DNA methylation and transcription factor availability: implications for developmental activation of the mouse Myogenin gene. | |
| | |
MedLine Citation:
|
PMID: 20498275 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
During development, gene activation is stringently regulated to restrict expression only to the correct cell type and correct developmental stage. Here, we present mechanistic evidence that suggests DNA methylation contributes to this regulation by suppressing premature gene activation. Using the mouse Myogenin promoter as an example of the weak CpG island class of promoters, we find that it is initially methylated but becomes demethylated as development proceeds. Full hypersensitive site formation of the Myogenin promoter requires both the MEF2 and SIX binding sites, but binding to only one site can trigger the partial chromatin opening of the nonmethylated promoter. DNA methylation markedly decreases hypersensitive site formation that now occurs at a detectable level only when binding to both MEF2 and SIX binding sites is possible. This suggests that the probability of activating the methylated promoter is low until two of the factors are coexpressed within the same cell. Consistent with this, the single-cell analysis of developing somites shows that the coexpression of MEF2A and SIX1, which bind the MEF2 and SIX sites, correlates with the fraction of cells that demethylate the Myogenin promoter. Taken together, these studies imply that DNA methylation helps to prevent inappropriate gene activation until sufficient activating factors are coexpressed. |
| | |
Authors:
|
Daniela Palacios; Dennis Summerbell; Peter W J Rigby; Joan Boyes |
Related Documents
:
|
12750705 - Aberrant methylation and impaired expression of the p15(ink4b) cell cycle regulatory ge... 18593905 - Frequent inactivation of a putative tumor suppressor, angiopoietin-like protein 2, in o... 12695555 - Profile of aberrant cpg island methylation along multistep gastric carcinogenesis. 18036775 - Diploid parthenogenetic embryos adopt a maternal-type methylation pattern on both sets ... 11528105 - Re-defining the chromatin loop domain. 8193125 - Structure and function in rhodopsin. 7. point mutations associated with autosomal domin... |
Publication Detail:
|
Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-05-24 |
Journal Detail:
|
Title: Molecular and cellular biology Volume: 30 ISSN: 1098-5549 ISO Abbreviation: Mol. Cell. Biol. Publication Date: 2010 Aug |
Date Detail:
|
Created Date: 2010-07-12 Completed Date: 2010-08-06 Revised Date: 2011-07-22 |
Medline Journal Info:
|
Nlm Unique ID: 8109087 Medline TA: Mol Cell Biol Country: United States |
Other Details:
|
Languages: eng Pagination: 3805-15 Citation Subset: IM |
Affiliation:
|
Section of Gene Function and Regulation, Institute of Cancer Research, London, United Kingdom. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals Binding Sites / genetics Chromatin CpG Islands DNA Methylation* Embryo, Mammalian Genes Homeodomain Proteins Methylation Mice Mice, Transgenic Myogenic Regulatory Factors Myogenin / genetics*, metabolism Transcription Factors / genetics, metabolism Transcriptional Activation |
| Chemical | |
Reg. No./Substance:
|
0/Chromatin; 0/Homeodomain Proteins; 0/Myogenic Regulatory Factors; 0/Myogenin; 0/SIX1 protein, human; 0/Transcription Factors; 0/myocyte-specific enhancer-binding factor 2 |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: A novel fluorescent sensor protein for visualization of redox states in the cytoplasm and in peroxis...
Next Document: HuR uses AUF1 as a cofactor to promote p16INK4 mRNA decay.