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Fetal Epigenetic Origins of Disease

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1 Fetal Epigenetic Origins of Disease
Chapter 45 Fetal Epigenetic Origins of Disease © 2015, Elsevier, Inc., Plant and Zeleznik, Knobil and Neill's Physiology of Reproduction, Fourth Edition

2 FIGURE 45.1 Epigenetic mechanisms: heritable chromatin state throughout replication and cell division. The epigenetic characteristics of a dividing cell must be passed on to the daughter cell. The mechanisms preserving the epigenetic landscape of the mother cell through cell division are unclear. However, the daughter cell requires that specific chromatin states are maintained, such as the packaging of telomeres and centromeres, in order to preserve genome stability. © 2015, Elsevier, Inc., Plant and Zeleznik, Knobil and Neill's Physiology of Reproduction, Fourth Edition

3 FIGURE 45. 2 Chromatin organization
FIGURE 45.2 Chromatin organization. (A) The nucleosome is the basic repeating unit of chromatin in all eukaryotes. The nucleosome consists of two copies of four histone proteins (H3, H4, H2A, and H2B), which form the histone octamer. The nucleosome is formed by 147 base pairs of DNA that wrap around the octamer. (B) Individual nucleosomes are separated from each other by short stretches of “linker DNA” that are not wrapped around the histone octamer. In order to undergo condensation to form heterochromatin, the nucleosomal array is aided by histone modifications such as histone methylation, as well as nonhistone proteins such as HP-1. © 2015, Elsevier, Inc., Plant and Zeleznik, Knobil and Neill's Physiology of Reproduction, Fourth Edition

4 FIGURE 45. 3 Epigenetics of fertilization
FIGURE 45.3 Epigenetics of fertilization. Both the sperm and the oocyte have distinct epigenetic landscapes that are essential for their role as gametes. However, upon fertilization both parental epigenomes must be reorganized in order to orchestrate the transcriptional program necessary for embryonic development. © 2015, Elsevier, Inc., Plant and Zeleznik, Knobil and Neill's Physiology of Reproduction, Fourth Edition

5 FIGURE 45.4 Maternal constraints: the developmental origins of adult health and disease (DOHaD). Many studies have shown that various maternal constraints are associated with the adult onset of metabolic disease such as exposure to in utero protein restriction, high fat diet, or famine. Epigenetic mechanisms may play a role in maintaining a memory of this in utero exposure until adulthood. © 2015, Elsevier, Inc., Plant and Zeleznik, Knobil and Neill's Physiology of Reproduction, Fourth Edition


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