Diving into Genetics and Genomics: Misconcept of Epigenetics

Monday, July 4, 2016

Misconcept of Epigenetics

There is a great buzz on twitter discussing what is epigenetics and what is not.

Epigenetics as a term is meaningless unless it refers to heritability. Otherwise it’s all transcriptional regulation @chrisw_thinkdox @nih
— Einstein Epigenomics (@EpgntxEinstein) April 8, 2016

I found this PNAS paper is worth to read: Epigenetis: Core misconcept

Some quotes from the paper:
Development is a process involves no changes of underlying DNA. It is driven primary by regulatory proteins called transcription factors (TFs) which binds to specific regulatory DNA sequence to activate or repress gene expression. This process starts from fertilized eggs where TFs are mainly contributed by mother.

In the first cell division these transcription factors are distributed asymmetrically to the daughter cells. Then, and in subsequent cell generations, new patterns of gene expression arise in two ways: as a matter of course (some transcription factors activating expression of genes encoding other regulatory proteins, etc.), and in response to signals sent by other cells. Signaling used in development affects expression of genes encoding yet more transcription factors—it does so by changing activities of transcription factors, already present, which target those genes. Retinoic acid (a small molecule) and growth hormone (a protein) are examples of such signaling molecules.

The Core Concepts Misconception

Curiously, the picture I have just sketched is absent from the Core Concepts article. Rather, it is said, chemical modifications to DNA (e.g., methylation) and to histones—the components of nucleosomes around which DNA is wrapped in higher organisms—drive gene regulation. This obviously cannot be true because the enzymes that impose such modifications lack the essential specificity: All nucleosomes, for example, “look alike,” and so these enzymes would have no way, on their own, of specifying which genes to regulate under any given set of conditions.

Histone modifications are called “epigenetic” in the Core Concepts article, a word that for years has implied memory (see Epigenetic). This is odd: It is true that some of these modifications are involved in the process of transcription per se—facilitating removal and replacement of nucleosomes as the gene is transcribed, for example (9, 10). And some are needed for certain forms of repression (11). But all attempts to show that such modifications are “copied along with the DNA,” as the article states, have, to my knowledge, failed.

Epigenetics involves two aspects: specificity and memory (heritability). In a word, it is not histone modification drives gene expression and histone modifications != epigenetics.

For more readings:

Another paper on Genetics: what do you mean: "epigenetic?"

Paper: Epigenetics, cellular memory and gene regulation

Two consecutive posts on Epigenetics: what is it and what isn't it?