The three HP1 (Heterochromatin Protein 1), HP1a, HP1b, and HP1g proteins are epigenetic markers of heterochromatin, the condensed, repressed form of chromatin. They are typically known to associate to the di-/tri-methylated lysine 9 of histone H3 (H3-K9me2/3), a repressive histone mark, HP1s are therefore linked to chromatin silencing. But on the other hand, HP1s are also linked to activated transcription, for example HP1g has been shown to localize within the body of coding genes in correlation with their transcriptional activity. Our laboratory has found implications of HP1g in the regulation of alternative splicing in conjunction with components of the RNA silencing machinery (1).
We are looking at the impact of chromatin on the regulation of transcription and transcription-associated processes, and we focus on the funtionality of the three HP1 protein isoforms in this context.
We have recently characterized a contribution of HP1g in the transcriptional regulation of stress and immunity genes in response to bacterial infection by the virulent bacteria Shigella (2). From the genes targeted by HP1g in this model, we are now dissecting the functional links between HP1 proteins and chromatin-associated RNA (pre-mRNA, long non-coding RNA,…) in the regulation of transcription. For this purpose we have designed a strategy for the genome-wide analysis of HP1-bound RNA, which may provide us with a global view on the different functionalities of HP1 in relationship with RNA.
(1). Ameyar-Zazoua M, Rachez C, Souidi M, Robin P, Fritsch L, Young R, Morozova N, Fenouil R, Descostes N, Andrau JC, Mathieu J, Hamiche A, Ait-Si-Ali S, Muchardt C, Batsché E, Harel-Bellan A. (2012) Argonaute proteins couple chromatin silencing to alternative splicing. Nat. Struct. Mol. Biol. 19:998-1004.
(2). Harouz H.*, Rachez C.*, Meijer BM., Marteyn B., Donnadieu F., Cammas F., Muchardt C., Sansonetti P., Arbibe L. (2014) Shigella flexneri targets the HP1γ subcode through the phosphothreonine lyase OspF. EMBO J. 33:2606-22.