The HP1α–CAF1–SetDB1‐containing complex provides H3K9me1 for Suv39‐mediated K9me3 in pericentric heterochromatin |
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Authors: | Alejandra Loyola Tiziana Bonaldi Danièle Roche Jean Pierre Quivy Axel Imhof Yoshihiro Nakatani Sharon Y R Dent Geneviève Almouzni |
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Affiliation: | 1. Fundación Ciencia para la Vida and Universidad San Sebastián, Avda Za?artu 1482, ?u?oa, Santiago, Chile;2. UMR218, CNRS/UPMC, Institut Curie, 26 Rue d'Ulm 75248, Paris Cedex 05, France;3. Department of Biochemistry and Molecular Biology, Unit 1000, The University of Texas, M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas, 77030 USA;4. Department of Experimental Oncology, European Institute of Oncology, Via Ademello 16, Milano, 20139 Italy;5. Histone Modifications Group and Munich Center of Integrated Protein Science, Schillerstrasse 44, 80336 Munich, Germany;6. Department of Cancer Biology, Dana‐Faber Cancer Institute and Harvard Medical School, SM 836, 44 Binney Street, Boston, Massachusetts, 02115 USA |
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Abstract: | Trimethylation of lysine 9 in histone H3 (H3K9me3) enrichment is a characteristic of pericentric heterochromatin. The hypothesis of a stepwise mechanism to establish and maintain this mark during DNA replication suggests that newly synthesized histone H3 goes through an intermediate methylation state to become a substrate for the histone methyltransferase Suppressor of variegation 39 (Suv39H1/H2). How this intermediate methylation state is achieved and how it is targeted to the correct place at the right time is not yet known. Here, we show that the histone H3K9 methyltransferase SetDB1 associates with the specific heterochromatin protein 1α (HP1α)–chromatin assembly factor 1 (CAF1) chaperone complex. This complex monomethylates K9 on non‐nucleosomal histone H3. Therefore, the heterochromatic HP1α–CAF1–SetDB1 complex probably provides H3K9me1 for subsequent trimethylation by Suv39H1/H2 in pericentric regions. The connection of CAF1 with DNA replication, HP1α with heterochromatin formation and SetDB1 for H3K9me1 suggests a highly coordinated mechanism to ensure the propagation of H3K9me3 in pericentric heterochromatin during DNA replication. |
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Keywords: | CAF1 H3K9 methylation HP1α pericentric heterochromatin SetDB1 |
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