NIH and Epigenomics

The NIH announced last week, that it will fund 22 grants on genome-wide studies of how epigenetic changes — chemical modifications to genes that result from diet, aging, stress, or environmental exposures — define and contribute to specific human diseases and biological processes. A 1) ___ is the complete set of DNA, in a cell. The epigenome consists of chemical compounds that modify, or mark, the genome in a way that tells it what to do, where to do it and when to do it. The marks, which are not part of the DNA itself, can be passed on from cell to cell as cells 2) ___, and from one generation to the next. The human body contains trillions of cells, all of which have essentially the same genome. Yet some cells are optimized for use in muscles, others for bones, the brain, the stomach and the rest of the body. Different sets of genes are turned on or off in various kinds of cells at different points in time. The epigenome influences which 3) ___ are active, and which proteins are produced in a particular cell. The epigenome signals, skin cells to behave like skin cells, same with heart cells, and all cells. The epigenome, marks the genome with its chemical tags. The epigenome also serves as the intersection between the genome and the 4) ___. The first type of mark, called DNA methylation, directly affects the DNA in a person’s genome. In this process, chemical tags called methyl groups attach to the backbone of the DNA 5) ___ in specific places. The methyl groups turn genes off or on by affecting interactions between DNA and the cell’s protein-making machinery. The second kind of mark, called histone modification, indirectly affects the DNA in the genome. Histones are spool-like 6) ___ that enable DNA’s very long molecules to be wound up neatly into chromosomes inside the cell nucleus. A variety of chemical tags can grab hold of the tails of histones, changing how tightly or loosely they package DNA. If the wrapping is tight, a gene may be hidden from the cell’s protein-making machinery, and consequently be switched off. In contrast, if the wrapping is loosened, a gene that was formerly hidden may be turned on. The chemical tags found on the DNA and histones of eggs and 7) ___ can be conveyed to the next generation. A genome contains two copies of every gene – one inherited from the mother and one from the father. For some genes, only the copy from the mother ever gets switched on, and for others, only the copy from the father. This pattern is called imprinting. The epigenome serves to distinguish between the two copies of an imprinted gene. For example, only the father’s copy of a gene called IGF2 is able to make its protein. That is because marks in the epigenome keep the mother’s IGF2 copy switched off in every cell of the body. Some diseases are caused by abnormal imprinting. Lifestyle and 8) ___ factors can expose a person to chemical tags that change the epigenome. The epigenome may change based on what a person eats and drinks, smokes, takes medicines, encounters pollutants, etc. There is also some evidence from animal and human studies that indicates that what a female eats and drinks during 9) ___ may change the epigenome of her offspring. Some epigenomic changes may trigger or increase the severity of disease. Researchers already have linked changes in the epigenome to various cancers, diabetes, autoimmune diseases and mental illnesses. A number of diseases and conditions to be studied under NIH grants will include tumor development, hardening of the arteries, autism, glaucoma, asthma, aging, and abnormal growth and development. These studies will help increase our understanding of how factors such as environmental exposures, alcohol, drug abuse and stress can modify the effect of epigenetics on diseases.

 

Answers: 1) genome; 2) divide; 3) genes; 4) environment; 5) molecules; 6) proteins; 7) sperm; 8) environmental; 9) pregnancy

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