000000435 001__ 435
000000435 005__ 20260227104217.0
000000435 0247_ $$2DOI$$a10.6083/M4NK3C08
000000435 037__ $$aETD
000000435 245__ $$aChanges in DNA methylation and histone modification during epigenetic transitions
000000435 260__ $$bOregon Health and Science University
000000435 269__ $$a2009
000000435 336__ $$aDissertation
000000435 502__ $$bPh.D.
000000435 520__ $$aAberrant epigenetic silencing is a major mechanism of tumor suppressor gene inactivation, yet the early events that trigger this process are not well defined. This work demonstrates that transient reductions in gene activation can initiate stable epigenetic silencing, producing chromatin changes similar to those seen at silenced tumor suppressor genes in cancer. Using an inducible transgene system and analysis of endogenous Aprt alleles, the study shows that silencing initiation depends on histone deacetylases, while DNA methylation primarily stabilizes later stages. The findings reveal distinct early and late silencing events and identify a heritable, DNA‑methylation–independent repressive state that limits stable reactivation.
000000435 540__ $$fCC BY
000000435 542__ $$fIn copyright - single owner
000000435 650__ $$aHistone Deacetylases$$020246
000000435 650__ $$aPhysiology$$024123
000000435 650__ $$aDNA Methylation$$031400
000000435 650__ $$aDNA$$017977
000000435 650__ $$aGenes, Tumor Suppressor$$028915
000000435 650__ $$aTranscriptional Activation$$028481
000000435 650__ $$aRegulatory Elements, Transcriptional$$036371
000000435 650__ $$aEpigenesis, Genetic$$035405
000000435 691__ $$aSchool of Medicine$$041369
000000435 692__ $$aDepartment of Molecular and Medical Genetics$$041428
000000435 7001_ $$aOyer, Jon$$uOregon Health and Science University$$041354
000000435 7201_ $$aTurker, Mitchell$$uOregon Health and Science University$$041354$$7Personal$$eAdvisor$$eMentor
000000435 8564_ $$959952368-b5b5-485c-abd4-3492a2b0916c$$s3734818$$uhttps://digitalcollections.ohsu.edu/record/435/files/436_etd.pdf$$ePublic$$2b0062efc463b685c4479118e6390b869$$31
000000435 905__ $$a/rest/prod/rr/17/1x/24/rr171x24p
000000435 909CO $$ooai:digitalcollections.ohsu.edu:435$$pstudent-work
000000435 956__ $$aGet Accessible Copy$$uhttps://ohsu.libwizard.com/f/requestaccessibledocument
000000435 980__ $$aTheses and Dissertations