Stories about: methylation

DNA methylation patterns linked to obesity and its complications

DNA methylation obesity
(Methylated DNA: Christoph Bock, Max Planck Institute for Informatics/Wikimedia Commons)

Why do some people seem to be prone to weight gain? Obesity has been linked to a variety of genetic changes, yet these differences don’t fully explain the variation in people’s body mass index (BMI). “Even though we’ve genetically sequenced more and more people at greater and greater breadth and depth, we haven’t completely explained who develops obesity and why,” says Michael Mendelson, MD, ScM, a pediatric cardiologist with Boston Children’s Hospital’s Preventive Cardiology Program.

Nor do prior studies explain why some overweight people develop health complications from obesity, like cholesterol problems, diabetes, hypertension and heart disease, while others don’t. Now comes strong evidence that an important factor is DNA methylation — a so-called epigenetic modification that influences whether genes are turned on or off.

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When reading genes, read the instructions first: Epigenetics and developmental disorders

The genome holds the instructions for making proteins, while the epigenome holds the instructions for reading the genes. Yang Shi wants to understand how those epigenetic instructions are read, especially in cases of intellectual disabilities. (JackBet/Flickr)

While the genome’s As, Ts, Cs, and Gs hold the instructions for making proteins, how does a cell know when to read a gene? And could it relate to developmental disorders?

These gene-reading instructions are encoded in our epigenome, a set of factors that give our cells exquisite control over when and where to turn individual genes on and off. This control involves a delicate and complex dance between DNA and proteins called histones – DNA wraps itself around histones to create a complex called chromatin – as well as the many different types of epigenetic tags.

Yang Shi, of the Division of Newborn Medicine at Children’s Hospital Boston, wants to understand what happens when the genome doesn’t read the epigenome’s instructions correctly, which in the developing brain can cause intellectual disabilities.

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Mapping out DNA’s extra bases

5-methylcytosine (L) and 5-hydroxymethylcytosine (R): the two DNA bases you didn't learn about in high school biology. (Image: Wikimedia Commons)

Adenine and thymine, cytosine and guanine. We all learned the names of the four DNA bases in high school biology class. But, just like the list of planets, the list of bases may not be set in stone.

Over the years, epigenetics researchers have identified two alternate forms of cytosine whose biology differs enough from that of their parent base that may count as fifth and sixth DNA bases. These additional cytosines, called 5-methylcytosine (5mc) and 5-hydroxymethylcytosine (5hmc), each have a group of atoms called a methyl group added onto their central ring, a feature normal cytosine lacks.

Apart from making biology textbook editors very unhappy, these two bases may play unique roles in biology. Adding methyl groups (or methylation “marks”) to cytosines and other components of the genome is a well-known epigenetic mechanism that gives the cell exquisite control of gene activity, which in turn greatly influences how the cell will behave. For instance, patterns of methylation marks on the genes of embryonic stem (ES) cells are linked the cells’ ability to develop into more mature cells. And the genomes of cancer cells often have methylation marks in the wrong places.

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