• Login
    View Item 
    •   Home
    • Theses and Dissertations
    • Theses and Dissertations
    • View Item
    •   Home
    • Theses and Dissertations
    • Theses and Dissertations
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Browse

    All of TUScholarShareCommunitiesDateAuthorsTitlesSubjectsGenresThis CollectionDateAuthorsTitlesSubjectsGenres

    My Account

    LoginRegister

    Help

    AboutPeoplePoliciesHelp for DepositorsData DepositFAQs

    Statistics

    Most Popular ItemsStatistics by CountryMost Popular Authors

    THE ROLE OF CIS- AND TRANS-ACTING FACTORS IN REGULATION OF DNA METHYLATION

    • CSV
    • RefMan
    • EndNote
    • BibTex
    • RefWorks
    Thumbnail
    Name:
    Madireddi_temple_0225E_12392.pdf
    Size:
    5.114Mb
    Format:
    PDF
    Download
    Genre
    Thesis/Dissertation
    Date
    2015
    Author
    Madireddi, Priyanka
    Advisor
    Issa, Jean-Pierre
    Committee member
    Sapienza, Carmen
    Liebermann, Dan A., 1949-
    Engel, Nora
    Bellacosa, Alfonso
    Department
    Molecular Biology and Genetics
    Subject
    Biology, Molecular
    Genetics
    Permanent link to this record
    http://hdl.handle.net/20.500.12613/1806
    
    Metadata
    Show full item record
    DOI
    http://dx.doi.org/10.34944/dspace/1788
    Abstract
    High level DNA methylation of promoter CpG islands (CGIs) represses gene expression. However, low-level CGI methylation is currently not distinguished from complete absence of methylation in the literature. Here we show that very low levels of methylation or methylation seeds (1-20%) on promoter CGIs is present in 5-20% of human genes and negatively correlates with gene expression in all tissues examined. In vitro, seeding directly represses reporter gene expression, an effect mediated by methyl-CpG-binding proteins as transient knockdown of MBD4 reverses this repression. In vivo, seeded genes are enriched for polycomb occupancy but seeding can also occur in H3K4me3 occupied promoters, where it also correlates with gene repression independently of Polycomb repressive complex binding. Seeded CGIs in normal WBCs are 19 fold and 65 fold more likely to gain hypermethylation in Acute Myelogenous Leukemia and Myelodysplastic Syndrome patients respectively, compared to unmethylated CGIs (i.e. those with <1% methylation). This study reveals a novel epigenetic mechanism of tissue specific methylation seeds that have strong effects on gene expression in healthy tissues, possess unique histone status, and predispose to gain of methylation in leukemias more so than previously known factors. In the second part, we analyzed the role of chromodomain protein CHD7 in CpG island methylator phenotype (CIMP) Colorectal Cancers (CRCs). Analysis of CHD7 target genes identified that frequently methylated genes in CIMP-positive CRCs have significantly higher enrichment of CHD7 occupancy in mouse neural stem cells and are among genes regulated by CHD7 in mouse embryonic stem cells. This study provides evidence for a causal link between CHD7 mutations in CRCs and the CIMP phenotype.
    ADA compliance
    For Americans with Disabilities Act (ADA) accommodation, including help with reading this content, please contact scholarshare@temple.edu
    Collections
    Theses and Dissertations

    entitlement

     
    DSpace software (copyright © 2002 - 2023)  DuraSpace
    Temple University Libraries | 1900 N. 13th Street | Philadelphia, PA 19122
    (215) 204-8212 | scholarshare@temple.edu
    Open Repository is a service operated by 
    Atmire NV
     

    Export search results

    The export option will allow you to export the current search results of the entered query to a file. Different formats are available for download. To export the items, click on the button corresponding with the preferred download format.

    By default, clicking on the export buttons will result in a download of the allowed maximum amount of items.

    To select a subset of the search results, click "Selective Export" button and make a selection of the items you want to export. The amount of items that can be exported at once is similarly restricted as the full export.

    After making a selection, click one of the export format buttons. The amount of items that will be exported is indicated in the bubble next to export format.