1 / 18

Chromatin Remodeling

Chromatin Remodeling. *Cytosine Methylation*. Glossary. Epigenetic: Heritable changes in gene function, not caused by changes in the DNA sequence itself.

adanne
Download Presentation

Chromatin Remodeling

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Chromatin Remodeling *Cytosine Methylation*

  2. Glossary Epigenetic:Heritable changes in gene function, not caused by changes in the DNA sequence itself. CpG (island):Stands for Cytosine (P-bond) Guanine. Refering to a small region of DNA with a high frequency of CG sequences with respect to other regions. Heterochromatin:Highly condensed, and transcription-suppressed sections of DNA Housekeeping Genes:Undergo active transcription for basic cell functions.

  3. Glossary – Enzymes DNMT:DNA Methyltransferase -1, 3a, 3b, L H3K9:Lysine 9 of Histone 3 Suv39h:histone methyltransferase (H3K9) MeCP/MBD:Methyl CpG Binding domain protein.

  4. Glossary – Enzymes HP1:Adaptor molecule. HDAC:Histone DeAcetylating protein PcG:Polycomb Group (and repressor complexes) EZH2, Eed, Su212:series of proteins that interact with PcG.

  5. Cytosine Methylation - Overview • A method of gene regulation and suppression. • Occurs when a methyl group is added to Carbon-5, of the pyrimidine ring via enzyme action. • An Epigenetic process • Methylation patterns are passed on to daughter strands during replication. • Closely linked to histone modification • Improper methylation can lead to the development of genetics disorders.

  6. Pattern of Inheritance • Function of DNMT 1 as a Maintenance Enzyme • CpG methylation only opposite another CpG which is already methylated. • Non-methylated CpG pairs are not recognized by DNMT 1

  7. Pattern of Inheritance (Molecular Biology Web Book: 2005)

  8. Identifying Methylation Sites • Bisulfate sequencing • Conversion of non-methyl. Cytosine to Uracil • No change to methyl. Cytosine • Sequenced through computer software identifying locations of methylation • Two concentrations of methylation (low or high)

  9. DNA & Histone Modification • Linkage between both DNA Methylation and Histone Modifications • Histone Deacetylation, Methylation • Which process is the initiator? • Self-reinforced Model

  10. The addition of methyl groups onto sites such as H3K9 The removal of acetyl groups from histone Loses neutral charge on molecule DNA & Histone Modification Methylation: Deacetylation:

  11. DNA & Histone Modification • Two opposite theories on which processes depends on which. • Theory: Histone Mod. depends on DNA methylation – DNMTs, MBDs recruiting HDAC • Theory: DNA methylation depends on Histone Mod. – Suv39h knockouts, requirements of a “reader” molecule. (Hp1)

  12. Self-Reinforced Model • Based on the idea DNA methylation and Histone Modification have a ‘flow’ of information. • Not a perfect model, does not fully explain gene silencing. However, a good explanation for permanent shut-off genes.

  13. Self-Reinforced Model • DNMT binds to HP1, DNA is methylated close to H3K9 site. • Causes MBD to bind with DNA, recruiting HDAC; H3K9 deacetylated. • MBD also attracts H3K9 methyltransferase and an additional HP1; H3K9 is methylated.

  14. Self-Reinforced Model

  15. Other DNA and Histone connections • H3K27 transcription repression (PcG, EED, EZH2 complex – “PRC” Polycomb Repressive Complex. • PRC involvement in X-inactivation, Hox gene silencing, cancer metastasis • H4K20 methylation. Lack of in some cancer cells

  16. Improper Methylation • Retts syndrome – loss of function MeCP2 (mental retardation in young girls) • ICF syndrome – DNMT3b mutation (abnormal immune system) • Total DNMT knockout in mice: fetus dies before birth • MBD2 assistance in hypermethylated cancer genes

  17. References: “A Simplified Description of DNA Methylation.” DNA Methylation Society. Oct 11, 2005. http://www.dnamethsoc.com/  Fuks, Francois. “DNA Methylation and histone modifications: teaming up to silence genes.” Current Opinion in Genetics. 15 (2005): 490-495 “[7] DNA Methylation and CpG Island.” Molecular Biology Web Book. 2005. http://www.web-books.com/MoBio/ “DNA Methylation.” Wikipedia, the Online Encyclopedia. 2005. http://en.wikipedia.org/wiki/DNA_methylation “Epigenetics.” Wikipedia, the Online Encyclopedia. 2005. http://en.wikipedia.org/wiki/Epigenetic “All HEPped Up about Methylation.” PLoS Biol 2(12): e433. November 23, 2004. http://biology.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pbio.0020433

  18. Questions? Comments? Slipper Limpets? ?

More Related