The histone tails have for decades been regarded as unstructured polypeptide
chains which simply served as molecular beacons to protein effectors which modify
chromatin. However some experimental evidence shows that the tails may contain
structure. Thus we conducted a Molecular Dynamics study of the Histone H3 tail and
itâs most important post translationally modified isoforms. The 500 ns experiments
showed the evolution of different secondary structure conformations for the different
modified isoforms. More interestingly the active isoform showed a statistically
significant longer reach compared to the inactive isoform. We next conducted a
molecular docking study of the 15 â residue tip of the H3 tail to the nucleosome
surface. The starting structures were sampled from the Molecular Dynamics
trajectories. The tips showed binding to nucleosome where the H3 tail exits the
nucleosome, between the DNA and the octamer. This binding position did not cha
nge between the different isoforms. We thus propose a molecular mechanism
whereby chromatin compaction is carried out at a nucleosome level, and is regulated
by transitions in the N-terminal H3 tail structures, which, in turn, are modulated by
specific epigenetic PTM patterns.
| Identifer | oai:union.ndltd.org:netd.ac.za/oai:union.ndltd.org:ufs/oai:etd.uovs.ac.za:etd-05272013-112146 |
| Date | 27 May 2013 |
| Creators | du Preez, Louis Lategan |
| Contributors | Prof MJH Hoffman, Prof H-G Patterton |
| Publisher | University of the Free State |
| Source Sets | South African National ETD Portal |
| Language | en-uk |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.uovs.ac.za//theses/available/etd-05272013-112146/restricted/ |
| Rights | unrestricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to University Free State or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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