Epigenetics by Dr.Chandan, how epigenetic changes influence embryos

Epigenetics in embryology. IVf

1. Epigenetics And Infertility Dr.Chandan.N Msc PhD EMB Clinical Embryologist and Scientific Director Certified by American College of Embryology

2. Topic of Discussion • Basic Concepts in Genetics • What is Epigenetic? • History of Epigenetic • How do epigenetics work? Mechanism of Epigenetics • Epigenetics and the Environment • Epigenetic Inheritance Epigenetic and Infertility

3. Cells are fundamental working units of every human being. All the instructions required to direct their activities are contained within the chemical deoxyribonucleic acid, also known as DNA. Basic Concepts in Genetics

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5. DNA from humans is made up of approximately 3 billion nucleotide bases. There are four fundamental types of bases that comprise DNA – adenine, cytosine, guanine, and thymine, commonly abbreviated as A, C, G, and T, respectively

6. The sequence , or the order, of the bases is what determines our life instructions. Interestingly enough, our DNA sequence is more than 99 percent similar to that of a chimpanzee. Less than 1 percent, or 15 million bases, has a distinctively different sequence that makes us human.

7. Within the 3 billion bases, there are about 20,000+ genes. Genes are specific sequences of bases that provide instructions on how to make important proteins –that trigger various biological actions to carry out life functions.

8. What is EPIGENETICS.? Epigenetics literally means "above" or "on top of" genetics. It refers to external modifications to DNA that turn genes "on" or "off." These modifications do not change the DNA sequence, but instead, they affect how cells "read" genes.

9. The term epigenetics refers to heritable changes in gene expression (active versus inactive genes) that does not involve changes to the underlying DNA sequence; i.e. a change in phenotype without a change in genotype. FOR EXAMPLE

10. Epigenetics is the reason : • Reason why a skin cell looks different from a brain cell or a muscle cell. All three cells contain the same DNA, but their genes are expressed differently . ( turned "on" or "off"), which creates the different cell types.

11. History The term epigenetics, which was coined by Conrad H. Waddington in 1942, was derived from the Greek word “epigenesis” which originally described the influence of genetic processes on development. Conrad H. Waddington and Ernst Hadorn , started the study of epigenetics

12. How do epigenetics work? An epigenome consists of a record of the chemical changes to the DNA and histone proteins of an organism; these changes can be passed down to an organism's offspring. Changes to the epigenome can result in changes to the structure of chromatin and changes to the function of the genome.

13. DNA holds the instructions for building the proteins that carry out a variety of functions in a cell. The epigenome is made up of chemical compounds and proteins that can attach to DNA and direct such actions as turning genes on or off , controlling the production of proteins in particular cells

14. When epigenomic compounds attach to DNA and modify its function, they are said to have "marked" the genome. These marks do not change the sequence of the DNA. Rather, they change the way cells use the DNA's instructions. The marks are sometimes passed on from cell to cell as cells divide. They also can be passed down from one generation to the next.

15. Mechanisms of Epigenetics DNA methylation Histone Modification Non-coding RNA (ncRNA)- 1 3 2

16. 1 DNA Methylation

17. Currently, DNA methylation is one of the most broadly studied and well-characterized epigenetic modifications dating back to studies done by Griffith and Mahler in 1969 which suggested that DNA methylation may be important in long term functioning.

18. A common type of epigenetic modification is called methylation. • Methylation involves attaching small molecules called methyl groups or a "chemical cap,". • each consisting of one carbon atom and three hydrogen atoms, to segments of DNA.

19. 2 Histone Modification

20. Histone modifications are proposed to affect chromosome function through at least two distinct mechanisms. The first mechanism suggests modifications may alter the electrostatic charge of the histone resulting in a structural change in histones or Second mechanism – the way they binds to DNA.

21. Histones proteins are the one that wraps around DNA . Without histones, DNA would be too long to fit inside cells. If histones squeeze DNA tightly, the DNA cannot be "read" by the cell. • Modifications that relax the histones can make the DNA accessible to proteins that "read“ genes .

22. Methylation of DNA and Histone causes Nucleosome to pack tightly together , Transcription factors cannot bind DNA and genes are not expressed Histone Acetylation result in loose packing of Nucleosome . Transcription factor can bind and express the gene

23. Non-Coding RNA ncRNA represent small RNA molecules encoded in the genomes of plants and animals. These highly conserved 22 nucleotides long RNA sequences regulate the expression of genes by binding to the 3'-untranslated regions (3'-UTR) of specific mRNAs. A growing body of evidence shows that ncRNAs are one of the key players in cell differentiation and growth, mobility and apoptosis (programmed cell death).

24. Epigenetics and the Environment

25. Epigenetic Inheritance

26. We used to think that a new embryo’s epigenome was completely erased and rebuilt from scratch. • But this isn't completely true. Some epigenetic tags remain in place as genetic information passes from generation to generation, a process called epigenetic inheritance.

27. It may be possible to pass down epigenetic changes to future generations if the changes occur in sperm or egg cells. Most epigenetic changes that occur in sperm and egg cells get erased when they two combine to form a fertilized egg, in a process called “ reprogramming .” This reprogramming allows the cells of the fetus to "start from scratch" and make their own epigenetic changes.

28. But this isn't completely true. Some epigenetic tags remain in place as genetic information passes from generation to generation, a process called epigenetic inheritance

29. Epigenetic and Infertility What lifestyle factors affect epigenetics? Several lifestyle factors have been identified that might modify epigenetic patterns, such as  diet, obesity, physical activity, tobacco smoking, alcohol consumption, environmental pollutants, psychological stress, and working on night shifts .

30. Thank you