Lecture 20 – Epigenomics – Animals

BIOL 5190/6190 Cellular & Molecular Singal TransductionPrepared by Bob Locy

Last modified -13F

Epigenetic Regulation by piwi-associated DNA methylation in Mammalian Germline

Bucher et al., (2012) Current Opinion in Plant Biology 15 (5): 503-510

Animal piwi-RNA and DNA methylation

In mammals, DNA methylation and demethylation are involved in diverse processes including:1. early embryogenesis

2. stem cell differentiation

3. genomic imprinting 75, 221,

Mayer W, Niveleau A, Walter J, Fundele R, Haaf T. Demethylation of the zygotic paternal genome. Nature 2000; 403:501–502.Haaf T. Methylation dynamics in the early mammalian embryo: implications of genome reprogramming defects for development. Curr Top Microbiol Immunol 2006; 310:13–22.

Watanabe D, Suetake I, Tada T, Tajima S. Stage- and cell-specific expression of Dnmt3a and Dnmt3b during embryogenesis. Mech Dev 2002; 118:187–190. Latham T, Gilbert N, Ramsahoye B. DNA methylation in mouse embryonic stem cells and development. Cell Tissue Res 2008; 331:31–55. 

Reik W, Walter J. Genomic imprinting: parental influence on the genome. Nat Rev Genet 2001; 2:21–32.Ideraabdullah FY, Vigneau S, Bartolomei MS. Genomic imprinting mechanisms in mammals. Mutat Res 2008; 647:77–85.

Animal piwi-RNA and DNA methylation (cont)

J.R., and Pikaard, C.S. 2011. Nature Reviews Molecular Cell Biology 12:483–492.

4. X chromosome inactivation

5. silencing of repetitive elements 224.

6. DNA methylation is also involved in regulating neuronal development and development of cancers 225, 226.

Heard E, Disteche CM. Dosage compensation in mammals: fine-tuning the expression of the X chromosome. Genes Dev 2006; 20:1848–1867. Senner CE, Brockdorff N. Xist gene regulation at the onset of X inactivation. Curr Opin Genet Dev 2009; 19:122–126.

Chen RZ, Pettersson U, Beard C, Jackson-Grusby L, Jaenisch R, DNA hypomethylation leads to elevated mutation rates. Nature 1998; 395:89–93. 

Dulac C. Brain function and chromatin plasticity. Nature 2010; 465:728–735. Feinberg AP, Ohlsson R, Henikoff S, The epigenetic progenitor origin of human cancer. Nat Rev Genet 2006; 7:21–33.

Feinberg AP et al. (2005) The epigenetic progenitor origin of human cancerNat Rev gene. 7: 21–33 doi:10.1038/nri1748

Figure 1 The clonal genetic model of cancer.

Feinberg AP et al. (2005) The epigenetic progenitor origin of human cancerNat Rev gene. 7: 21–33 doi:10.1038/nri1748

Figure 2 The epigenetic progenitor model of cancer.

Genomic and epigenomic regualtion of adipose tissue inflammation in obesity

Toubal et al. Trends in Endocrinology & Metabolism, 2013

Genomic and epigenomic regualtion of adipose tissue inflammation in obesity

Toubal et al. Trends in Endocrinology & Metabolism, 2013

Genomic and epigenomic regualtion of adipose tissue inflammation in obesity

Toubal et al. Trends in Endocrinology & Metabolism, 2013

Genomic and epigenomic regualtion of adipose tissue inflammation in obesity

Toubal et al. Trends in Endocrinology & Metabolism, 2013