Global ETD Search
Search theses and dissertations gathered from participating repositories worldwide. Every result links back to the library that holds it. No account is needed.
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Showing 1 to 10 of 10 for “"Bromodomains"”.
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A ‘bump-&-hole’ approach for engineering allele-selective inhibition of the BET bromodomains
… chemical genetic work is the BET family of bromodomains – 8 closely related, and structurally conserved, epigenetic acetyl-lysine reader domains that so far has defied single-bromodomain inhibition. The Alessio Ciulli lab has previously designed a proof-of-concept ‘bump-&-hole’ system to …
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Epigenetic regulation of gene expression by BRD4 in cancer and innate immune response
… of histone and non-histone proteins via their bromodomains (BDs). This interaction either changes the availabilities of cis-regulatory elements by altering chromatin compacity or activates specific transcription factors, both of which contribute to transcriptional activation of BRD4’s target …
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Multiple Functions of BRD4 in E2 Mediated HPV Transciptional Regulation
… of HPV transcription. Brd4 contains two bromodomains which function as acetyl-lysine-binding modules that facilitate chromatin targeting via their interactions with acetylated histones. Although Brd4 has been known to be involved in E2-mediated transcriptional regulation, it was unclear …
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Quantitative approaches to probe the acetylproteome
… and computational methods were developed. Bromodomains were engineered to explore binding preferences using degenerate peptide arrays as well as develop acetyllysine affinity reagents as an alternative to anti-acetyllysine antibodies. Additionally, bioorthogonal proteomics were employed to …
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Identification of the ERK5 Kinase as a Key Regulator of Embryonic Stem Cell Pluripotency
… compounds which inhibit both ERK5 and BET family bromodomains drive ESCs from the naïve state towards primed pluripotency. Using compound selectivity engineering and CRISPR/Cas9 genome editing, I deconvolve distinct functions for ERK5 and BRD4 in pluripotency regulation. Furthermore, I show that …
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Predictive Modelling of the Primary and Secondary Pharmacology of Compounds in Drug Discovery
… co-crystal structures for new ligands bound to bromodomains, as well as literature evidence. The PCM technique can be used in virtual screening, in silico off-target panel screening of compounds and to aid future structure-based design. The second section of this thesis is concerned with the …
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SWI/SNF COMPLEXES COORDINATE WITH HISTONE MODIFICATIONS TO REGULATE CHROMATIN REMODELING
… Owing to the presence of acetyl-lysine binding bromodomains in these complexes and to a greater extent in RSC the differences in their remodeling activities, if any, were expected to be accentuated by histone acetylation. Studies with H3 and H4 tail acetylated nucleosomes provided evidence for …
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Molecular regulation of BRD3 in forward programming of Megakaryocytes
Platelets are one of the most abundant cell type in the blood, and they play a crucial role in the process of homeostasis. Platelet traits, such as platelet count (PLT) and mean platelet volume (MPV) are highly heritable and stable within individuals, but the molecular mechanisms controlling these …
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Development of peptide-based 19F MRI agents and BPTF-bromodomain inhibitors
Molecular imaging is the process of using targeted probes to detect abnormalities at the molecular level by observing interactions to specific biomarkers. Magnetic resonance imaging (MRI) presents an interesting avenue with respect to development of probes for the early detection of disease. In …
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THE PHD FINGER OF SP140: A STRUCTURAL AND FUNCTIONAL STUDY
… seems to retain the characteristic ability of bromodomains to bind to acetylated histone tails, despite it does not show the conserved Tyr, Tyr and Asn residues employed by bromodomains in order to bind to acetylated lysines. If confirmed, these results suggest that Sp140 bromodomain is …