Degree Type
Dissertation
Date of Award
2012
Degree Name
Doctor of Philosophy
Department
Biochemistry, Biophysics and Molecular Biology
First Advisor
Michael A Shogren-Knaak
Abstract
Heterochromatin is a higher order unique compacted chromatin structure present at the centromeres and the telomeres of chromosomes. It is characterized by the methylation of histone H3 on lysine 9 and the binding of a key structural and functional protein called heterochromatin protein 1 (HP1) to that histone mark. The structural determinants for such binding were not clear. In this study, we show that in vitro HP1 can bind to uniformly H3-K9 methylated nucleosomal arrays in a methylation dependent fashion, and this binding promotes the formation of a more compacted structure. This binding is shown to be dependent on the ability of HP1 to form a dimeric structure through its chromoshadow domain and also upon its ability to bind methylated lysine through its chromo domain. Also, HP1 has shown some ability for non-specific DNA-dependent binding to unmethylated arrays under certain conditions. The more specific methylation dependent binding is shown to promote intra-molecular and inter-molecular compaction of methylated arrays. In vivo, we show that the ability of HP1 to bind methylated lysine and to dimerize is essential for its in vivo functionality. Using molecular modeling we show that HP1 can adopt several binding positions to methylated arrays without steric hindrance.
DOI
https://doi.org/10.31274/etd-180810-2735
Copyright Owner
Abdelhamid Azzaz
Copyright Date
2012
Language
en
Date Available
2012-10-31
File Format
application/pdf
File Size
81 pages
Recommended Citation
Azzaz, Abdelhamid, "Understanding Higher Order Heterochromatin Structure And Its Determinants" (2012). Graduate Theses and Dissertations. 12266.
https://lib.dr.iastate.edu/etd/12266