Molecular basis of histone H3K36me3 recognition by the PWWP domain of Brpf1

Vezzoli, Alessandro; Bonadies, Nicolas; Allen, Mark D.; Freund, Stefan; Santiveri, Clara M.; Kvinlaug, Brynn T.; Huntly, Brian J. P.; Göttgens, Berthold; Bycroft, Mark

doi:10.1038/nsmb.1797

Cited by 195 publications

(226 citation statements)

References 19 publications

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“…Specialized chromatin regulatory factors named "chromatin readers" (66) specifically recognize distinct histone signatures on the chromatin, thereby defining the functional consequence of histone methylation. Several PWWP-containing proteins interact via their PWWP domain with specific histone modifications; the PWWP domain of Pdp1 (PWWP domain protein 1) specifically interacts with H4K20me1 (57), the PWWP domain of plant homeodomain finger-containing protein 1 (BRPF1) (64) and DNA methyltransferase 3a (65) interact with H3K36me3 (40,84), and the PWWP domain of N-PAC, MSH-6, NSD1, and NSD2 interacts with H3K36me3 (66). We thus analyzed lentiviral integration preference near specific epigenetic marks.…”

Section: H2azmentioning

confidence: 99%

Role of the PWWP Domain of Lens Epithelium-derived Growth Factor (LEDGF)/p75 Cofactor in Lentiviral Integration Targeting

Gijsbers

Vets

Rijck

et al. 2011

Journal of Biological Chemistry

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LEDGF/p75 is a chromatin-interacting, cellular cofactor of HIV integrase that dictates lentiviral integration site preference. In this study we determined the role of the PWWP domain of LEDGF/p75 in tethering and targeting of the lentiviral pre-integration complex, employing potent knockdown cell lines allowing analysis in the absence of endogenous LEDGF/p75. Deletion of the PWWP domain resulted in a diffuse subnuclear distribution pattern, loss of interaction with condensed chromatin, and failure to rescue proviral integration, integration site distribution, and productive virus replication. Substitution of the PWWP domain of LEDGF/p75 with that of hepatoma-derived growth factor or HDGF-related protein-2 rescued viral replication and lentiviral integration site distribution in LEDGF/p75-depleted cells. Replacing all chromatin binding elements of LEDGF/p75 with full-length hepatoma-derived growth factor resulted in more integration in genes combined with a preference for CpG islands. In addition, we showed that any PWWP domain targets SMYD1-like sequences. Analysis of integration preferences of lentiviral vectors for epigenetic marks indicates that the PWWP domain is critical for interactions specifying the relationship of integration sites to regions enriched in specific histone post-translational modifications.Stable integration of the viral DNA into the host genome is one of the hallmarks of retroviral replication and has profound consequences for both the virus and the host. For the virus it is essential to direct integration in the host cell chromatin to sites that allow efficient gene expression to fulfill a successful infection cycle. Retroviruses from different genera have evolved to integrate their genomic DNA at different sites in the genome of their respective hosts. Human immunodeficiency virus (HIV) and other lentiviruses have a strong preference for integration in active transcription units (1), and murine leukemia virus (MLV) genomes preferentially integrate near transcription start sites and CpG island regions (2), whereas avian sarcoma leukosis virus (3, 4) and the human T-cell leukemia virus display a much weaker preference for these features (5, 6), only weakly favoring integration in active transcription units. Deciphering the mechanisms that dictate integration site selection is instrumental to better understand basic retrovirology and its clinical applications such as drug development and gene therapy.Studies of yeast retrotransposons demonstrated that cellular cofactors determine the integration site preference (7-9). Likewise, interactions between HIV integrase (IN) 4 and the host cell protein lens epithelium-derived growth factor (LEDGF/p75) (10) direct HIV integration targeting. LEDGF/p75 specifically binds IN via its integrase binding domain (LEDGF ) ( Fig. 1) and functions as a molecular tether during lentiviral integration, bridging the viral pre-integration complex (PIC) with the host cell chromatin (11-13). Cells depleted for LEDGF/p75 (13, 14) or somatic knock-out cells (15, 1...

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Section: H2azmentioning

confidence: 99%

Role of the PWWP Domain of Lens Epithelium-derived Growth Factor (LEDGF)/p75 Cofactor in Lentiviral Integration Targeting

Gijsbers

Vets

Rijck

et al. 2011

Journal of Biological Chemistry

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“…The following spectra were recorded to obtain backbone and side chain resonance assignments (16): two-dimensional 1 H, 15 N HSQC, three-dimensional triple resonance spectra HNCO, HN(CA)CO, CBCA(CO)NH, CBCANH, HBHA-(CO)NH, C(CO)NH-TOCSY H(CCO)NH-TOCSY, two-dimensional 13 Structure Calculation and Validation-The NOE crosspeaks from the three-dimensional 15 N-and 13 C-separated NOESYs were assigned and converted into distance restraints. Dihedral angle restraints for the and angles were derived from N, CO, CA, CB, and HA chemical shifts by using TALOS (18).…”

Section: Methodsmentioning

confidence: 99%

“…Bromodomains interact with acetylated lysines on N-terminal tails of histones and other proteins (12), and the PWWP domain of BRPF1 has been shown to bind histone H3K36me3 (13). PHD fingers were shown to recognize methylated or unmethylated lysine 4 of histone H3 (14,15).…”

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confidence: 99%

Recognition of Unmodified Histone H3 by the First PHD Finger of Bromodomain-PHD Finger Protein 2 Provides Insights into the Regulation of Histone Acetyltransferases Monocytic Leukemic Zinc-finger Protein (MOZ) and MOZ-related factor (MORF)

Jin

Zhang

et al. 2011

Journal of Biological Chemistry

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MOZ (monocytic leukemic zinc-finger protein) and MORF (MOZ-related factor) are histone acetyltransferases important for HOX gene expression as well as embryo and postnatal development. They form complexes with other regulatory subunits through the scaffold proteins BRPF1/2/3 (bromodomain-PHD (plant homeodomain) finger proteins 1, 2, or 3). BRPF proteins have multiple domains, including two PHD fingers, for potential interactions with histones. Here we show that the first PHD finger of BRPF2 specifically recognizes the N-terminal tail of unmodified histone H3 (unH3) and report the solution structures of this PHD finger both free and in complex with the unH3 peptide. Structural analysis revealed that the unH3 peptide forms a third antiparallel ␤-strand that pairs with the PHD1 two-stranded antiparallel ␤-sheet. The binding specificity was determined primarily through the recognition of arginine 2 and lysine 4 of the unH3 by conserved aspartic acids of PHD1 and of threonine 6 of the unH3 by a conserved asparagine. Isothermal titration calorimetry and NMR assays showed that post-translational modifications such as H3R2me2as, H3T3ph, H3K4me, H3K4ac, and H3T6ph antagonized the interaction between histone H3 and PHD1. Furthermore, histone binding by PHD1 was important for BRPF2 to localize to the HOXA9 locus in vivo. PHD1 is highly conserved in yeast NuA3 and other histone acetyltransferase complexes, so the results reported here also shed light on the function and regulation of these complexes.Histone acetyltransferases (HATs) 3 are enzymes that catalyze the transfer of an acetyl group from acetyl-CoA to the ⑀-amino groups of lysine on histones, which results in important regulatory effects in chromatin structure and assembly as well as gene expression. HATs are highly diverse and generally form multiprotein complexes. Different HAT complexes are composed of various unique subunits, and the combination of these subunits contributes to the unique features of each HAT complex (1).MOZ (monocytic leukemic zinc-finger protein) and MORF (MOZ-related factor), a pair of large HATs of the MYST (Moz, Ybf2/Sas3, Sas2, Tip60) family, are important for hematopoiesis, skeletogenesis, neurogenesis, and other developmental processes, and they also have been implicated in leukemogenic and other tumorigenic progressions (2). A recent study in mice embryos reported that MOZ is required for normal levels of spatially correct Hox gene expression and for correct body segment identity. MOZ is specifically required for the H3K9 acetylation of active Hox gene loci (3). MOZ is also required for the maintenance of hematopoietic stem cells and plays a role in the differentiation of erythroid and myeloid cells (4). By contrast, MORF is required for the maintenance of undifferentiated neuronal progenitors and for adult neural stem cell self-renewal and neuronal differentiation (5). MOZ and MORF genes are often translocated in acute myeloid leukemia cells, producing either fusion proteins with CBP (cAMP-response elementbinding protein (CREB)-bind...

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“…H3K36me3 and SETD2 have been demonstrated to regulate both transcriptional elongation and alternative splicing events (Wagner and Carpenter, 2012). Several proteins have been reported to read H3K36me3 modifications by virtue of possessing a PWWP domain, including DNMT3a and Brpf1 (Dhayalan et al, 2010;Vezzoli et al, 2010;Wu et al, 2011). A recent report described for the first time, a reader for H3.3-specific K36me3 called BS69/ZMYND11 (Wen et al, 2014c).…”

Section: H33k36m and Tumorigenesismentioning

confidence: 99%

Histone Variant H3.3: A versatile H3 variant in health and in disease

Xiong

Wen

2016

Sci. China Life Sci.

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Histones are the main protein components of eukaryotic chromatin. Histone variants and histone modifications modulate chromatin structure, ensuring the precise operation of cellular processes associated with genomic DNA. H3.3, an ancient and conserved H3 variant, differs from its canonical H3 counterpart by only five amino acids, yet it plays essential and specific roles in gene transcription, DNA repair and in maintaining genome integrity. Here, we review the most recent insights into the functions of histone H3.3, and the involvement of its mutant forms in human diseases.histone variants, H3.3, histone chaperones, development, tumorigenesis

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Molecular basis of histone H3K36me3 recognition by the PWWP domain of Brpf1

Cited by 195 publications

References 19 publications

Role of the PWWP Domain of Lens Epithelium-derived Growth Factor (LEDGF)/p75 Cofactor in Lentiviral Integration Targeting

Role of the PWWP Domain of Lens Epithelium-derived Growth Factor (LEDGF)/p75 Cofactor in Lentiviral Integration Targeting

Recognition of Unmodified Histone H3 by the First PHD Finger of Bromodomain-PHD Finger Protein 2 Provides Insights into the Regulation of Histone Acetyltransferases Monocytic Leukemic Zinc-finger Protein (MOZ) and MOZ-related factor (MORF)

Histone Variant H3.3: A versatile H3 variant in health and in disease

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