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Capturing chromatin-associated proteins in nucleosomal context
Koutná, Eliška ; Veverka, Václav (advisor) ; Hlouchová, Klára (referee) ; Bařinka, Cyril (referee)
| 9 ABSTRACT Eukaryotic DNA is stored in the nucleus wrapped around histone octamers in the form of nucleosomes. These basic chromatin units can further associate with DNA-binding factors through DNA and the N-terminal histone tails that are subjected to various covalent posttranslational modifications that, in combination with DNA modifications, define the epigenetic code. Eukaryotic transcription is dependent on these specific histone modifications - their recognition by chromatin reader proteins triggers complex processes relying on the coordinated association of transcription regulatory factors. Although various modification states of a particular histone residue often lead to differential outcomes, it is not entirely clear how they are discriminated at a molecular level. Moreover, the contribution of intrinsically disordered regions outside of the specialized reader domains to nucleosome binding remains unexplored. In this thesis, the main focus is put on the transcription coactivator LEDGF/p75, capable of reading the H3K36me2/3 histone mark, and the pioneer transcription factor Sox2. Using structural biological and biophysical techniques, the interaction of LEDGF and Sox2 with nucleosomes is dissected, describing the peculiarities of intrinsically disordered DNA interacting motifs. Two...
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