Understanding Higher Order Heterochromatin Structure And Its Determinants

TL;DRAbstract

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 uniformlyH3-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-mol

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