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dc.contributor.advisorGarcia, Benjamin Aen_US
dc.contributor.authorBritton, Laura-Maeen_US
dc.contributor.otherMolecular Biology Departmenten_US
dc.description.abstractHistone post translational modifications (PTMs) are a key component of the dynamic and responsive nucleoprotein structure that is chromatin. Assorted physiological processes such as transcription and DNA repair are regulated by these histone PTMs and their governing enzymes, as well as by the nucleosomal structure at the local gene site. Downstream of signaling cascades, histone modifying enzymes can be recruited to add specific histone marks, which serve as recruitment sites for DNA-binding proteins, transcription factors, and chromatin remodeling complexes, which in turn modulate transcription of crucial genes. With each new year, different histone marks are unveiled with equally novel or groundbreaking physiological capabilities, which prompt two key questions: (1) what other critical marks are there to be identified and (2) what new mechanisms of chromatin function can be elucidated by characterizing these novel variations within a prevalently studied biological system. In this study, quantitative mass spectrometry was employed to identify novel serine, threonine and tyrosine O-acteylation on histones. In the contexts of cellular reprogramming and cell cycle progression, histone H3 serine 10 acetylation (H3S10ac) was observed to be enriched in pluripotent mouse embryonic stem cells and during the DNA synthesis (S) phase of cell cycle. Chromatin Immunoprecipitation followed by high-throughput DNA sequencing (ChIP-Seq) revealed an enrichment of homeobox sequences at H3S10ac sites within the genome. In vitro histone acetyltransferase (HAT) reactions, coupled with in vivo chemical inhibition, uncovered p300, CREB-binding protein (CBP) and fungal Rtt109 as unique H3S10ac HATs. Although H3S10ac is an invariably lower abundance mark, its enrichment in stem cells compared to differentiated cells, mainly within homeobox motifs reiterates the precision of HAT enzymes for selecting their targets, as well as the potential impact of even lower level histone marks in epigenetic regulation. This discovery opens a doorway to further understanding epigenetic regulation in the context of cellular differentiation, and will hopefully encourage future studies of both combinatorial and individual histone modifications.en_US
dc.publisherPrinceton, NJ : Princeton Universityen_US
dc.relation.isformatofThe Mudd Manuscript Library retains one bound copy of each dissertation. Search for these copies in the <a href=> library's main catalog </a>en_US
dc.subjecthistone post translational modificationsen_US
dc.subjectmass spectrometryen_US
dc.subject.classificationMolecular biologyen_US
dc.titleSerine, Threonine and Tyrosine O-Acetylation in the Chromatin Landscapeen_US
dc.typeAcademic dissertations (Ph.D.)en_US
Appears in Collections:Molecular Biology

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