Structure of the Chromo Barrel Domain from the MOF Acetyltransferase

Nielsen, Peter R.; Nietlispach, Daniel; Buscaino, Alessia; Warner, Rosemary J.; Akhtar, Asifa; Murzin, Alexey G.; Murzina, Natalia V.; Laue, Ernest D.

doi:10.1074/jbc.m501347200

Cited by 50 publications

(64 citation statements)

References 35 publications

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“…Chromodomains have been implicated in binding methylated lysine residues and nucleic acids (reviewed in reference 9), and the chromodomains from the MSL3 and MRG15 proteins could form an aromatic cage implicated in methyl-lysine binding (27,43) and may be required for MSL3 binding to RNA or single-stranded DNA (40). In light of these considerations, the existence of truncated forms of hMSL3L1 that lack an amino-terminal chromodomain was unexpected.…”

Section: Discussionmentioning

confidence: 99%

A Human Protein Complex Homologous to the Drosophila MSL Complex Is Responsible for the Majority of Histone H4 Acetylation at Lysine 16

Smith

Cayrou

Huang³

et al. 2005

Molecular and Cellular Biology

300

256

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We describe a stable, multisubunit human histone acetyltransferase complex (hMSL) that contains homologs of the Drosophila dosage compensation proteins MOF, MSL1, MSL2, and MSL3. This complex shows strong specificity for histone H4 lysine 16 in chromatin in vitro, and RNA interference-mediated knockdown experiments reveal that it is responsible for the majority of H4 acetylation at lysine 16 in the cell. We also find that hMOF is a component of additional complexes, forming associations with host cell factor 1 and a protein distantly related to MSL1 (hMSL1v1). We find two versions of hMSL3 in the hMSL complex that differ by the presence of the chromodomain. Lastly, we find that reduction in the levels of hMSLs and acetylation of H4 at lysine 16 are correlated with reduced transcription of some genes and with a G 2 /M cell cycle arrest. This is of particular interest given the recent correlation of global loss of acetylation of lysine 16 in histone H4 with tumorigenesis.The dynamic regulation of chromatin structure can be brought about by a complex series of posttranslational modifications to histones, particularly on the amino-terminal histone tails (33,48). Among the lysines that can be acetylated, lysine 16 of histone H4 appears to be uniquely targeted in a number of organisms. Studies of telomeric silencing in Saccharomyces cerevisiae have shown that lysine 16-specific acetyltransferase and deacetylase activities determine the boundaries of silenced chromatin (32, 59). Furthermore, chromatin immunoprecipitation and site-directed mutagenesis in budding yeast clearly indicate that acetylation of H4 lysine 16 has an independent specific function in relation to gene transcription when compared to other histone acetylation sites (16,34). In Drosophila, lysine 16 acetylation is targeted to the hypertranscribed male X chromosome in the process of dosage compensation (8,35). Biochemical analysis of bulk histones in mammalian cells has indicated that most of the monoacetylated H4 is acetylated at lysine 16, as is most of the di-and triacetylated forms, leading to the suggestion that this is the first acetylation mark on H4 or possibly the last to be taken off (61, 69). One rationale for a special role for lysine 16 acetylation is that it is the only known site of acetylation in the basic patch of H4, a region from amino acids 16 to 20 that is implicated in the formation of higher-order chromatin structure (17). Recently, loss of acetylation at lysine 16 of histone H4 has been identified as a common hallmark of human cancer (22).In Drosophila, dosage compensation-the equalization of X-linked gene products in males and females-is achieved by enhancing the transcriptional level of X-linked genes in males.Five genes involved in this process were identified due to male-specific lethality when mutated (4,5,26). These genes are male-specific lethal 1 (msl1), msl2, msl3, maleless (mle), and males-absent on the first (mof). All five gene products form the MSL complex, which harbors histone acetyltransferase (HAT) activity with...

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Section: Discussionmentioning

confidence: 99%

A Human Protein Complex Homologous to the Drosophila MSL Complex Is Responsible for the Majority of Histone H4 Acetylation at Lysine 16

Smith

Cayrou

Huang³

et al. 2005

Molecular and Cellular Biology

300

256

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“…The results indicated that the SAWADEE domains could be divided into two conserved motifs, each of which may adopt a structure similar to that of the chromo barrel domain (Fig. S6C), a domain family that is similar to the classic chromo domain in sequence but adopts a β-barrel instead of the α + β fold of the chromo domain (27). A subset of the proteins containing chromo barrel or chromo domains has been shown to bind methylated histones and the interaction involves 3-4 conserved aromatic residues that form an "aromatic-cage" to pocket the methylated lysine from histones (28)(29)(30).…”

Section: Loci Where Sirnas But Not Dna Methylation Is Reduced In the mentioning

confidence: 99%

DTF1 is a core component of RNA-directed DNA methylation and may assist in the recruitment of Pol IV

Zhang

Yang

Zeng

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

164

179

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DNA methylation is an important epigenetic mark in many eukaryotic organisms. De novo DNA methylation in plants can be achieved by the RNA-directed DNA methylation (RdDM) pathway, where the plant-specific DNA-dependent RNA polymerase IV (Pol IV) transcribes target sequences to initiate 24-nt siRNA production and action. The putative DNA binding protein DTF1/SHH1 of Arabidopsis has been shown to associate with Pol IV and is required for 24-nt siRNA accumulation and transcriptional silencing at several RdDM target loci. However, the extent and mechanism of DTF1 function in RdDM is unclear. We show here that DTF1 is necessary for the accumulation of the majority of Pol IV-dependent 24-nt siRNAs. It is also required for a large proportion of Pol IV-dependent de novo DNA methylation. Interestingly, there is a group of RdDM target loci where 24-nt siRNA accumulation but not DNA methylation is dependent on DTF1. DTF1 interacts directly with the chromatin remodeling protein CLASSY 1 (CLSY1), and both DTF1 and CLSY1 are associated in vivo with Pol IV but not Pol V, which functions downstream in the RdDM effector complex. DTF1 and DTF2 (a DTF1-like protein) contain a SAWADEE domain, which was found to bind specifically to histone H3 containing H3K9 methylation. Taken together, our results show that DTF1 is a core component of the RdDM pathway, and suggest that DTF1 interacts with CLSY1 to assist in the recruitment of Pol IV to RdDM target loci where H3K9 methylation may be an important feature. Our results also suggest the involvement of DTF1 in an important negative feedback mechanism for DNA methylation at some RdDM target loci.histone modifications | small RNA | gene silencing | transposon D NA cytosine methylation is a conserved epigenetic mark that plays important roles in maintaining genome stability, transcriptional gene silencing, and developmental regulation (1, 2). In plants, DNA methylation occurs in three sequence contexts: CG, CHG, and CHH (H = A, C, T). CG and CHG methylation are symmetric in sequence and are maintained through a semiconservative mechanism that requires the DNA methyltransferases (METHYLTRANSFERASE 1) (MET1) and CHROMOMETHYLASE 3 (CMT3), respectively. In contrast, the asymmetric CHH methylation needs to be established during each cell cycle (1, 2). In plants a 24-nt small interfering RNA (siRNA)-dependent DNA methylation pathway is involved in recruiting the de novo DNA methyltransferase DOMAINS REARRANGED METHYLASE 2 (DRM2) and is responsible for DNA methylation at many transposable elements and repetitive sequences (3, 4).Two plant-specific homologs of RNA polymerase II play important roles in the RNA-directed DNA methylation (RdDM) pathway (5). RNA polymerase IV presumably initiates 24-nt siRNA biogenesis by specifically transcribing RdDM target loci to produce single-stranded RNA (ssRNA) transcripts, which serve as templates for RNA-dependent RNA polymerase 2 (RDR2) to generate double-stranded RNAs (dsRNAs). CLASSY 1 (CLSY1), a putative ATP-dependent chromatin remodeling protein, is prop...

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“…These observations are consistent with the far-UV circular dichroism data. In this context, it would be interesting to note that recently a putative nuclear CD from MOF, a member of the histone acetylating transferase from Drosophila, has been shown to have a ␤-barrel structure without the C-terminal helix conventionally found in the structures of CDs (28). Hydrogenbonding interactions between residues located in ␤-strands I and III (Thr 13 -NH, strand I) to Val 34 -CO (strand III) and Val 34 -NH (strand III)…”

Section: Description Of the Three-dimensional Structures Of Cds Of Cpmentioning

confidence: 99%

Three-Dimensional Solution Structures of the Chromodomains of cpSRP43

Vaithiyalingam

Kumar

Leena

et al. 2005

Journal of Biological Chemistry

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Chloroplasts contain a unique signal recognition particle (cpSRP). Unlike the cytoplasmic forms, the cpSRP lacks RNA but contains a conserved 54-kDa GTPase and a novel 43-kDa subunit (cpSRP43). Recently, three functionally distinct chromodomains (CDs) have been identified in cpSRP43. In the present study, we report the three-dimensional solution structures of the three CDs (CD1, CD2, and CD3) using a variety of triple resonance NMR experiments. The structure of CD1 consists of a triple-stranded ␤-sheet segment. The C-terminal helical segment typically found in the nuclear chromodomains is absent in CD1. The secondary structural elements in CD2 and CD3 include a triple-stranded antiparallel ␤-sheet and a C-terminal helix. Interestingly, the orientation of the C-terminal helix is significantly different in the structures of CD2 and CD3. Critical comparison of the structures of the chromodomains of cpSRP43 with those found in nuclear chromodomain proteins revealed that the diverse protein-protein interactions mediated by the CDs appear to stem from the differences that exist in the surface charge potentials of each CD. Results of isothermal titration calorimetry experiments confirmed that only CD2 is involved in binding to cpSRP54. The negatively charged C-terminal helix in CD2 possibly plays a crucial role in the cpSRP54-cpSRP43 interaction.Chloroplasts are the site of photosynthesis and various other important metabolic processes. Most of the proteins required for the function and maintenance of the chloroplasts are encoded in the nucleus, synthesized in the cytoplasm, and imported into the stroma by general import machinery (1, 2). The routing of proteins from the stroma to the thylakoid membrane occurs via one of four different targeting pathways (3). The post-translational transport of a family of light-harvesting chlorophyll a/b-binding integral membrane proteins (LHCPs) 2 from the stroma to the thylakoid occurs predominantly via the chloroplast signal recognition particle (cpSRP)-mediated pathway (4, 5).CpSRP differs significantly from all other signal recognition particle systems (4 -6). Unlike cytosolic signal recognition particles from eukaryotes and prokaryotes, cpSRP is not a ribonucleoprotein. It lacks RNA and contains a novel 43-kDa subunit that interacts with its substrates post-translationally. CpSRP is a heterodimer consisting of a 54-kDa subunit and a 43-kDa subunit (7). A recent study (8) revealed that the cpSRP43 interaction site is unique to cpSRP54 and is not present in the SRP54 subunit of other signal recognition particle systems.The cpSRP43 subunit is composed of two types of structural motifs, ankyrin repeats and chromodomains (chromosome organization modifier) (4, 9, 10). Ankyrin repeats are one of the most frequently observed amino acid motifs in the protein data base (11,12). Ankyrin repeats are a stable modular domain (of ϳ33 amino acids) scaffold that are tailored for molecular interaction. Ankyrin repeats have a well defined structure and canonical helix-loop-helix ␤-hairpin-loop f...

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Structure of the Chromo Barrel Domain from the MOF Acetyltransferase

Cited by 50 publications

References 35 publications

A Human Protein Complex Homologous to the Drosophila MSL Complex Is Responsible for the Majority of Histone H4 Acetylation at Lysine 16

A Human Protein Complex Homologous to the Drosophila MSL Complex Is Responsible for the Majority of Histone H4 Acetylation at Lysine 16

DTF1 is a core component of RNA-directed DNA methylation and may assist in the recruitment of Pol IV

Three-Dimensional Solution Structures of the Chromodomains of cpSRP43

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