Genome-wide target identification of sequence-specific transcription factors through ChIP sequencing

dc.contributor.advisorIyer, Vishwanath R.en
dc.contributor.committeeMemberDeLozanne, Arturoen
dc.contributor.committeeMemberMarcotte, Edwarden
dc.contributor.committeeMemberTucker, Philipen
dc.contributor.committeeMemberStevens, Scotten
dc.creatorLee, Bum Kyuen
dc.date.accessioned2011-11-17T22:04:33Zen
dc.date.accessioned2017-05-11T22:23:45Z
dc.date.available2011-11-17T22:04:33Zen
dc.date.available2017-05-11T22:23:45Z
dc.date.issued2011-05en
dc.date.submittedMay 2011en
dc.date.updated2011-11-17T22:04:50Zen
dc.descriptiontexten
dc.description.abstractThe regulation of gene expression at the right time, place, and degree is crucial for many cellular processes such as proliferation and development. In addition, in order to maintain cellular life, cells must rapidly and appropriately respond to various environmental stimuli. Sequence-specific transcription factors (TFs) can recognize functional regulatory DNA elements in a sequence-specific manner so that they can regulate only a specific group of genes, a process which enables cells to cope with diverse internal and external stimuli. Human has approximately 1,400 sequence-specific TFs whose aberrant expression causes a wide range of detrimental consequences including developmental disorders, diseases, and cancers; therefore, it is pivotal to identify the binding sites of each sequence-specific TF in order to unravel its roles in and mechanisms of gene regulation. Even though some TFs have been intensively studied, the majority of TFs still remain to be studied, particularly the tasks of identifying their genome-wide target genes and deciphering their biological roles in specific cellular contexts. Many questions remain unanswered: how many sites on the human genome a sequence-specific TF can bind; whether all TF-bound sites are functional; how a TF achieves binding specificity onto its targets; how and to what extent a TF is involved in gene regulation. Comprehensive identification of the binding sites of sequence-specific TFs and follow-up molecular studies including gene expression microarrays will provide close answers to these questions. Chromatin Immunoprecipitation coupled with recently developed high-throughput sequencing (ChIP-seq) allows us to perform genome-scale unbiased identification of the binding sites of sequence-specific TFs. Here, to gain insight into gene regulatory functions of TFs as well as their influences on gene expression, we conducted, in diverse cell lines, genome-wide identification of the binding sites of several sequence-specific TFs (CTCF, E2F4, MYC, Pol II) that are involved in a wide range of biological functions, including cell proliferation, development, apoptosis, genome stability, and DNA repair. Analysis of ChIP-seq data provided not only comprehensive binding profiles of those TF across the genome in diverse cell lines, but also revealed tissue-specific binding of CTCF, MYC, and Pol II as well as combinatorial usage among these three factors. Analyses also showed that some CTCF binding sites were inherited from parents to children and regulated in an individual-specific as well as allele-specific manner. Finally, genome-wide target identification of several TFs will broaden our understanding of the gene regulatory roles of these sequence-specific TFs.en
dc.description.departmentMicrobiologyen
dc.format.mimetypeapplication/pdfen
dc.identifier.slug2152/ETD-UT-2011-05-3038en
dc.identifier.urihttp://hdl.handle.net/2152/ETD-UT-2011-05-3038en
dc.language.isoengen
dc.subjectSequence-specific transcription factorsen
dc.subjectGenome-wide target genesen
dc.subjectCellular contextsen
dc.subjectBinding sitesen
dc.subjectChromatin Immunopracipitationen
dc.subjectChIP-seq dataen
dc.subjectE2F4en
dc.subjectCTCFen
dc.subjectMYCen
dc.subjectRNAPIIen
dc.titleGenome-wide target identification of sequence-specific transcription factors through ChIP sequencingen
dc.type.genrethesisen

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