Epigenetic mechanisms of gene regulation

1. Epigenetic mechanisms of gene regulation • Chromatin structure • Slows transcription • Hypercondensation stops transcription • Position effect variegation • X inactivation • Inactivation of one X chromosome in female mammals • Genomic imprinting • Silences transcription selectively if inherited from one parent

2. Normal chromatin structure slows transcription Fig. 17.13

3. Remodeling of chromatin mediates the activation of transcription Fig. 17.13

4. Studies using DNase identify decompacted regions Fig. 12.12 a

5. Extreme condensation silences expression • Heterochromatin • Darkly stained region of chromosome • Highly compacted even during interphase • Usually found in regions near centromere • Constitutive heterochromatin remains condensed most of time in all cells (e.g., Y chromosomes in flies and humans) • Euchromatin • Lightly stained regions of chromosomes • Contains most genes

6. Heterochromatin versus euchromatin • Heterochromatin is darkly stained • Euchromatin is lightly stained • C-banding techniques stains constitutive heterochromatin near centromere Fig. 12.13

7. Hypercondensation over chromatin domains causes transcriptional silencing Fig. 17.14

8. Position effect variegation in Drosophila: moving a gene near heterochromatin prevents it expression • Facultative heterochromatin • Moving a gene near heterochromatin silences its activity in some cells and not others Fig. 12.14 a

9. Position effect variegation in Drosophila: moving a gene near heterochromatin prevents it expression • A model for position-effect variegation • Heterochromatin can spread different distances in different cells Fig. 12.14 b

10. In mammals hypercondensation is often associated with methylation • It is possible to determine the methylation state of DNA using restriction enzymes that recognize the same sequence, but are differentially sensitive to methylation Fig. 17.14

11. X inactivation • Inactivation of one X chromosome to control for dosage compensation in female mammals • One X chromosome appears in interphase cells as a darkly stained heterochromatin mass-Barr body

12. Experiments with transmission of Ig f2 deletion showed mice inheriting deletion from male were small. Mice inheriting deletion from female were normal. Figure 17.15 a

13. Figure 17.15 b

14. H19 promoter is methylated during spermatogenesis and thus the H19 promoter is not available to the enhancer and is not expressed Figure 17.15 d

15. Methylation can be maintained across generations by methylases that recognize methyl groups on one strand and respond by methylating the opposite strand Fig. 17.15 c

16. Figure 17.15 e