epigenetic mechanisms of gene regulation

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

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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 - PowerPoint PPT Presentation

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Page 1: Epigenetic mechanisms of gene regulation

Epigenetic mechanisms of gene regulationEpigenetic mechanisms of gene regulation

Chromatin structureChromatin structure Slows transcriptionSlows transcription Hypercondensation stops transcriptionHypercondensation stops transcription Position effect variegationPosition effect variegation

X inactivationX inactivation Inactivation of one X chromosome in female mammalsInactivation of one X chromosome in female mammals

Genomic imprintingGenomic imprinting Silences transcription selectively if inherited from one Silences transcription selectively if inherited from one

parentparent

Page 2: Epigenetic mechanisms of gene regulation

Normal chromatin structure slows Normal chromatin structure slows transcriptiontranscription

Fig. 17.13

Page 3: Epigenetic mechanisms of gene regulation

Remodeling of chromatin mediates Remodeling of chromatin mediates the activation of transcriptionthe activation of transcription

Fig. 17.13

Page 4: Epigenetic mechanisms of gene regulation

Studies using DNase identify Studies using DNase identify decompacted regionsdecompacted regions

Fig. 12.12 a

Page 5: Epigenetic mechanisms of gene regulation

Extreme condensation silences Extreme condensation silences expressionexpression

HeterochromatinHeterochromatin Darkly stained region of chromosome Darkly stained region of chromosome Highly compacted even during interphaseHighly compacted even during interphase Usually found in regions near centromereUsually found in regions near centromere Constitutive heterochromatin remains condensed most Constitutive heterochromatin remains condensed most

of time in all cells (e.g., Y chromosomes in flies and of time in all cells (e.g., Y chromosomes in flies and humans)humans)

EuchromatinEuchromatin Lightly stained regions of chromosomesLightly stained regions of chromosomes Contains most genesContains most genes

Page 6: Epigenetic mechanisms of gene regulation

Heterochromatin versus euchromatinHeterochromatin versus euchromatin

Heterochromatin Heterochromatin is darkly stainedis darkly stained

Euchromatin is Euchromatin is lightly stainedlightly stained

C-banding C-banding techniques stains techniques stains constitutive constitutive heterochromatin heterochromatin near centromerenear centromere

Fig. 12.13

Page 7: Epigenetic mechanisms of gene regulation

Hypercondensation over chromatin domains Hypercondensation over chromatin domains causes transcriptional silencingcauses transcriptional silencing

Fig. 17.14

Page 8: Epigenetic mechanisms of gene regulation

Position effect variegation in Drosophila: moving a Position effect variegation in Drosophila: moving a gene near heterochromatin prevents it expressiongene near heterochromatin prevents it expression

Facultative Facultative heterochromatinheterochromatin Moving a gene Moving a gene

near near heterochromatin heterochromatin silences its silences its activity in some activity in some cells and not cells and not othersothers

Fig. 12.14 a

Page 9: Epigenetic mechanisms of gene regulation

A model for A model for position-effect position-effect variegationvariegation Heterochromatin Heterochromatin

can spread can spread different distances different distances in different cellsin different cells

Position effect variegation in Drosophila: moving a Position effect variegation in Drosophila: moving a gene near heterochromatin prevents it expressiongene near heterochromatin prevents it expression

Fig. 12.14 b

Page 10: Epigenetic mechanisms of gene regulation

In mammals hypercondensation is In mammals hypercondensation is often associated with methylationoften associated with methylation

It is possible to determine the methylation state of It is possible to determine the methylation state of DNA using restriction enzymes that recognize the DNA using restriction enzymes that recognize the same sequence, but are differentially sensitive to same sequence, but are differentially sensitive to methylationmethylation

Fig. 17.14

Page 11: Epigenetic mechanisms of gene regulation

X inactivationX inactivation

Inactivation of one X chromosome to Inactivation of one X chromosome to control for dosage compensation in female control for dosage compensation in female mammalsmammals One X chromosome appears in interphase cells One X chromosome appears in interphase cells

as a darkly stained heterochromatin mass-Barr as a darkly stained heterochromatin mass-Barr bodybody

Page 12: Epigenetic mechanisms of gene regulation

Experiments with transmission of Experiments with transmission of Ig fIg f 22 deletion showed mice inheriting deletion from deletion showed mice inheriting deletion from male were small. Mice inheriting deletion from male were small. Mice inheriting deletion from female were normal.female were normal.

Figure 17.15 a

Page 13: Epigenetic mechanisms of gene regulation

Figure 17.15 b

Page 14: Epigenetic mechanisms of gene regulation

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

Page 15: Epigenetic mechanisms of gene regulation

Methylation can be maintained across generations Methylation can be maintained across generations by methylases that recognize methyl groups on one by methylases that recognize methyl groups on one strand and respond by methylating the opposite strand and respond by methylating the opposite strandstrand

Fig. 17.15 c

Page 16: Epigenetic mechanisms of gene regulation

Figure 17.15 e