Epigenetic markers strongly affect binding of transcription factors
Excerpt: “The same epigenetic marks can be read as “keep off” or “welcome,” depending on what DNA-binding protein, or transcription factor, is doing the reading. These marks, methylated cytosine and guanine dinucleotides (mCpGs), normally indicate which portions of the genome are inactive. But new findings from a systematic study of hundreds of transcription factors suggest that mCpGs may play a more subtle role in gene regulation.
In this new study, scientists based at Karolinska Institutet systematically analyzed the binding specificities of transcription factors to DNA that was marked by mCpGs, as well as to DNA that was unmarked by mCpGs. The observed that mCpGs can influence binding of most transcription factors to DNA—in some cases negatively and in others positively.
Interestingly, many of the transcription factors that prefer to bind to mCpG sites appear to be important to development. This finding may inform future analyses of the role of DNA methylation on cell differentiation, chromatin reprogramming, and transcriptional regulation.
The results pave the way for cracking the genetic code that controls the expression of genes, and will have broad implications for the understanding of development and disease. The availability of genomic information relevant to disease is expanding at an exponentially increasing rate.
“This study identifies how the modification of the DNA structure affects the binding of transcription factors, and this increases our understanding of how genes are regulated in cells and further aids us in deciphering the grammar written into DNA,” noted Professor Taipale.””
Excerpt from the original study:
“One shortcoming is the lack of knowledge about DNA binding specificities (motifs) for hundreds of the estimated ~1600 human transcription factors. Another is how transcription factor binding is modulated by “epigenetics”—a contentious term that refers to heritable states of both cells and organisms, as well as the covalent chemical modifications of DNA and protein that often provide the underlying mechanism. DNA methylation at cytosine and guanine dinucleotides (mCG) satisfies most views of epigenetics, as it is inherited across cell divisions and functions in imprinting (parent-of-origin–dependent gene expression). On page 502 of this issue, Yin et al. provide a comprehensive look at the extent to which human transcription factor binding is affected by mCG, and make a striking finding: Many homeodomain transcription factors—perhaps the best characterized developmental regulators in biology can bind to specific methylated DNA sequences.
More generally, the study of Yin et al. contributes a unique perspective to evaluating how transcription factors bind DNA. Transcription factor motif modeling is critical for the study of global gene regulation, allowing us to predict potential binding sites in the genome. Given that so many transcription factors are affected by chemical modifications to DNA, we are now faced with a clear necessity to incorporate DNA methylation into motif models, and a new type of data from which to learn to read the genome the way transcription factors do.”
My comment: This study confirms my previous claims about factors affecting phenotypes of organisms and observed changes in nature. Alterations in organisms are based on epigenetic factors and designed mechanisms mediated by nutrition, stress, climate and other environmental factors. Even one addition or deletion of one methyl group on a gene might have a significant influence on cell activity and identity. Random mutations or natural selection have no role in biodiversity. There are no mechanisms for large scale evolution. Everything points to God’s design and creation.