Nucleosome compaction facilitates HP1γ binding to methylated H3K9

Abstract

The α, β and γ isoforms of mammalian heterochromatin protein 1 (HP1) selectively bind to methylated lysine 9 of histone H3 via their chromodomains. Although the phenotypes of HP1-knockout mice are distinct for each isoform, the molecular mechanisms underlying HP1 isoform-specific function remain elusive. In the present study, we found that in contrast to HP1α, HP1γ could not bind tri-methylated H3 lysine 9 in a reconstituted tetra-nucleosomes when the nucleosomes were in an uncompacted state. The hinge region connecting HP1's chromodomain and chromoshadow domain contributed to the distinct recognition of the nucleosomes by HP1α and HP1γ. HP1γ, but not HP1α, was strongly enhanced in selective binding to tri-methylated lysine 9 in histone H3 by the addition of Mg2+ or linker histone H1, which are known to induce compaction of nucleosomes. We propose that this novel property of HP1γ recognition of lysine 9 in the histone H3 tail in different nucleosome structures plays a role in reading the histone code.

In vivo epigenetic editing of sema6a promoter reverses impaired transcallosal connectivity caused by C11orf46/ARL14EP neurodevelopmental risk gene

“…Recently, the SET (histone methyltransferase) domain-containing transcriptional repressor, PRDM8, was described as essential for the formation of trans-callosal and other interhemispheric fiber tracts 44 Likewise, heterochromatin-associated protein HP1γ is required for the crossing of callosal axons into the contralateral hemisphere, while increased neuronal HP1γ expression promotes growth and differentiation of dendrites and axons 45 . Interestingly, PRDM8 promotes H3K9 methylation 46 and HP1γ is bound preferentially to compacted nucleosomal arrays bearing the repressive H3K9me3 mark 47 . Furthermore, the C11orf46-binding partner and repressive H3K9MTAse, SETDB1, has been implicated in transcriptional regulation of S-type clustered Protocadherin genes, a group of cell adhesion molecules broadly important for neuronal connectivity 48 .…”

Prefrontal cortex expression of chromatin modifier genes in male WSP and WSR mice changes across ethanol dependence, withdrawal, and abstinence

“…Interestingly, chromobox protein homolog 3 ( Cbx3 ), that encodes for the protein heterochromatin protein 1γ (HP1γ), was expressed in WSP mice at levels more than 3-fold higher than in WSR mice. CBX3 (HP1γ) localizes to euchromatin or to both euchromatin and heterochromatin, and it may bind H3K9, leading to the condensation of chromatin, but it may also be associated with induction of gene transcription (Canzio, Larson, and Narlikar, 2014; Kwon and Workman, 2011; Mishima et al, 2015). Given the prominent role of this gene in modulating transcription, it may be a good candidate to explore in order to understand the phenotypic differences in alcohol response of these two mouse lines.…”

RFTS‐dependent negative regulation of Dnmt1 by nucleosome structure and histone tails

“…After incubation at 37°C for 1 h, the reaction mixtures were separated by 7% SDS/PAGE. Proteins were stained with Lumitein (Biotium, Inc, CA, USA), and bands were detected with a fluoro-imager, FLA9500, as described by Mishima et al [43]. The percentage of shifted Dnmt1 over input Dnmt1 was calculated.…”