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内容記述 |
HP1s are involved in the assembly of heterochromatin and transcriptional regulation. Here, we report the molecular mechanisms underlying binding of chromoshadow domain of HP1γ (HP1γCSD) to transcriptional co-repressor KAP1 and the HP1γ self-assembly. Using crystallography, NMR and mass photometry we show that HP1γCSD recognizes the HP1 box of KAP1 (KAP1Hbox) and forms a relatively stable dimer of dimers, assembled in an antiparallel manner, in contrast to the corresponding HP1αCSD complex that shows concentration-dependent oligomerization and the arrangement of HP1αCSD protomers in a parallel manner. The β-sheet interface between HP1γCSD dimers is stabilized through electrostatic interactions, unlike the hydrophobic β-sheet interface of HP1αCSD. In vivo rescue experiments using KAP1 and HP1s knock out mouse embryonic stem cells (ESCs) reveal a unique cooperative action of KAP1 and the HP1γ isoform, but not other HP1s, in the repression of the long noncoding RNA (lncRNA) AI662270, underscoring the notion that cellular functions of HP1 proteins are not redundant. |
