👤 Christian Muchardt

Heterochromatin protein 1 (HP1) proteins are chromatin-bound transcriptional regulators. While their chromodomain binds histone H3 methylated on lysine 9, their chromoshadow domain associates with the H3 histone fold in a region involved in chromatin remodeling. Here, we show that phosphorylation at histone H3 threonine 45 and serine 57 within this latter region differentially affects binding of the three mammalian HP1 isoforms HP1α, HP1β and HP1γ. Both phosphorylation events are dependent on the activity of the DYRK1A kinase that antagonizes HP1-mediated transcriptional repression and participates in abnormal activation of cytokine genes in Down's syndrome-associated megakaryoblastic leukemia. Show less

The mammalian heterochromatin protein 1 (HP1) family of proteins was recently shown to be involved in transient repression of inducible promoters. One of these promoters is the HIV1 long terminal repeat, which, during viral latency, recruits a non-processive RNA polymerase II (RNAPII) that synthesizes a short regulatory transcript. Here, we have used this promoter to examine the interplay of HP1alpha, HP1beta and HP1gamma with RNAPII. We find that, in the absence of stimulation, HP1beta is present on the promoter together with the non-processive RNAPII and functions as a negative regulator. On activation, HP1beta bound to methylated H3K9 is rapidly released concurrent with histone H3 phospho-acetylation, and is replaced by HP1gamma. This isoform localizes to the promoter but also inside the coding region, together with the processive RNAPII. Our data show that HP1 recruitment-release is a sequential mechanism that is precisely regulated and highly dependent on transcription. Show less