Plasticity of HP1 proteins in mammalian cells

Abstract

We have compared the distribution of endogenous heterochromatin protein 1 (HP1) proteins (α, β and γ) in different epithelial lines, pluripotent stem cells and embryonic fibroblasts. In parallel, we have interrogated assembly and dynamics of newly expressed HP1-GFP proteins in cells lacking both HP1α and HP1β alleles, blocked at the G1-S boundary, or cultured in the presence of HDAC and HAT inhibitors. The results reveal a range of cell type and differentiation state-specific patterns that do not correlate with `fast' or `slow' subunit exchange in heterochromatin. Furthermore, our observations show that targeting of HP1γ to heterochromatic sites depends on HP1α and H1β and that, on an architectural level, HP1α is the most polymorphic variant of the HP1 family. These data provide evidence for HP1 plasticity under shifting microenvironmental conditions and offer a new conceptual framework for understanding chromatin dynamics at the molecular level.

Histone H4 lysine 20 monomethylation promotes transcriptional repression by L3MBTL1

“…This implies that L3MBTL1 mediates repression in the context of an H4K20me1 mark in facultative heterochromatin (that lacks acetylation). The nuclear distribution of L3MBTL1 and H4K20me1, and the identification of HP1g, a protein linked to facultative heterochromatin, in the L3MBTL1 complex further support our inference (Sims et al, 2006;Dialynas et al, 2007;Trojer et al, 2007).…”

Drosophila HP1c isoform interacts with the zinc-finger proteins WOC and Relative-of-WOC to regulate gene expression

“…Moreover, ubiquitously expressed HP1 isoforms show differential chromosomal distributions, as HP1a is mainly associated to heterochromatin, while HP1c is excluded from centromeric heterochromatin and HP1b is found both at euchromatic and heterochromatic domains (Smothers and Henikoff 2001). A similar situation is observed in mammals, where the patterns of localiza-tion of the three HP1 isoforms (HP1␣, HP1␤, and HP1␥) overlap only partially and show differential dynamics during differentiation and cell cycle progression (Minc et al 1999;Hayakawa et al 2003;Dialynas et al 2007). On the other hand, in the nematode Caenorhabditis elegans, two HP1 isoforms exist (HPL1 and HPL2), showing preferential euchromatic association, partially nonoverlapping expression and localization patterns, and distinct mutant phenotypes Schott et al 2006).…”

Differential contribution of HP1 proteins to DNA end resection and homology-directed repair

“…Beyond the evolutionary aspect, the context of cancer cells will be particularly interesting to consider given that frequent unbalance between HP1 paralogs is observed. 25 In addition, we should also consider the important role that HP1 proteins play in transcriptional regulation 12 and examine whether the different phenotypes observed herein could also be related, at least in part, to indirect transcriptional modulation of relevant DDR genes. Thus, transcriptome analysis under conditions of specific knockdown of the different HP1 paralogs would provide an entry point into this question that would then deserve a comprehensive study.…”