共查询到20条相似文献,搜索用时 15 毫秒
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Nielsen PR Nietlispach D Mott HR Callaghan J Bannister A Kouzarides T Murzin AG Murzina NV Laue ED 《Nature》2002,416(6876):103-107
Specific modifications to histones are essential epigenetic markers---heritable changes in gene expression that do not affect the DNA sequence. Methylation of lysine 9 in histone H3 is recognized by heterochromatin protein 1 (HP1), which directs the binding of other proteins to control chromatin structure and gene expression. Here we show that HP1 uses an induced-fit mechanism for recognition of this modification, as revealed by the structure of its chromodomain bound to a histone H3 peptide dimethylated at Nzeta of lysine 9. The binding pocket for the N-methyl groups is provided by three aromatic side chains, Tyr21, Trp42 and Phe45, which reside in two regions that become ordered on binding of the peptide. The side chain of Lys9 is almost fully extended and surrounded by residues that are conserved in many other chromodomains. The QTAR peptide sequence preceding Lys9 makes most of the additional interactions with the chromodomain, with HP1 residues Val23, Leu40, Trp42, Leu58 and Cys60 appearing to be a major determinant of specificity by binding the key buried Ala7. These findings predict which other chromodomains will bind methylated proteins and suggest a motif that they recognize. 相似文献
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Active genes are tri-methylated at K4 of histone H3 总被引:92,自引:0,他引:92
Santos-Rosa H Schneider R Bannister AJ Sherriff J Bernstein BE Emre NC Schreiber SL Mellor J Kouzarides T 《Nature》2002,419(6905):407-411
Lysine methylation of histones in vivo occurs in three states: mono-, di- and tri-methyl. Histone H3 has been found to be di-methylated at lysine 4 (K4) in active euchromatic regions but not in silent heterochromatic sites. Here we show that the Saccharomyces cerevisiae Set1 protein can catalyse di- and tri-methylation of K4 and stimulate the activity of many genes. Using antibodies that discriminate between the di- and tri-methylated state of K4 we show that di-methylation occurs at both inactive and active euchromatic genes, whereas tri-methylation is present exclusively at active genes. It is therefore the presence of a tri-methylated K4 that defines an active state of gene expression. These findings establish the concept of methyl status as a determinant for gene activity and thus extend considerably the complexity of histone modifications. 相似文献
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Rb targets histone H3 methylation and HP1 to promoters 总被引:78,自引:0,他引:78
Nielsen SJ Schneider R Bauer UM Bannister AJ Morrison A O'Carroll D Firestein R Cleary M Jenuwein T Herrera RE Kouzarides T 《Nature》2001,412(6846):561-565
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Zhou Z Feng H Zhou BR Ghirlando R Hu K Zwolak A Miller Jenkins LM Xiao H Tjandra N Wu C Bai Y 《Nature》2011,472(7342):234-237
The centromere is a unique chromosomal locus that ensures accurate segregation of chromosomes during cell division by directing the assembly of a multiprotein complex, the kinetochore. The centromere is marked by a conserved variant of conventional histone H3 termed CenH3 or CENP-A (ref. 2). A conserved motif of CenH3, the CATD, defined by loop 1 and helix 2 of the histone fold, is necessary and sufficient for specifying centromere functions of CenH3 (refs 3, 4). The structural basis of this specification is of particular interest. Yeast Scm3 and human HJURP are conserved non-histone proteins that interact physically with the (CenH3-H4)(2) heterotetramer and are required for the deposition of CenH3 at centromeres in vivo. Here we have elucidated the structural basis for recognition of budding yeast (Saccharomyces cerevisiae) CenH3 (called Cse4) by Scm3. We solved the structure of the Cse4-binding domain (CBD) of Scm3 in complex with Cse4 and H4 in a single chain model. An α-helix and an irregular loop at the conserved amino terminus and a shorter α-helix at the carboxy terminus of Scm3(CBD) wraps around the Cse4-H4 dimer. Four Cse4-specific residues in the N-terminal region of helix 2 are sufficient for specific recognition by conserved and functionally important residues in the N-terminal helix of Scm3 through formation of a hydrophobic cluster. Scm3(CBD) induces major conformational changes and sterically occludes DNA-binding sites in the structure of Cse4 and H4. These findings have implications for the assembly and architecture of the centromeric nucleosome. 相似文献
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A PHD finger of NURF couples histone H3 lysine 4 trimethylation with chromatin remodelling 总被引:1,自引:0,他引:1
Wysocka J Swigut T Xiao H Milne TA Kwon SY Landry J Kauer M Tackett AJ Chait BT Badenhorst P Wu C Allis CD 《Nature》2006,442(7098):86-90
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Recognition of unmethylated histone H3 lysine 4 links BHC80 to LSD1-mediated gene repression 总被引:1,自引:0,他引:1
Lan F Collins RE De Cegli R Alpatov R Horton JR Shi X Gozani O Cheng X Shi Y 《Nature》2007,448(7154):718-722
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Fischle W Tseng BS Dormann HL Ueberheide BM Garcia BA Shabanowitz J Hunt DF Funabiki H Allis CD 《Nature》2005,438(7071):1116-1122
Tri-methylation of histone H3 lysine 9 is important for recruiting heterochromatin protein 1 (HP1) to discrete regions of the genome, thereby regulating gene expression, chromatin packaging and heterochromatin formation. Here we show that HP1alpha, -beta, and -gamma are released from chromatin during the M phase of the cell cycle, even though tri-methylation levels of histone H3 lysine 9 remain unchanged. However, the additional, transient modification of histone H3 by phosphorylation of serine 10 next to the more stable methyl-lysine 9 mark is sufficient to eject HP1 proteins from their binding sites. Inhibition or depletion of the mitotic kinase Aurora B, which phosphorylates serine 10 on histone H3, causes retention of HP1 proteins on mitotic chromosomes, suggesting that H3 serine 10 phosphorylation is necessary for the dissociation of HP1 from chromatin in M phase. These findings establish a regulatory mechanism of protein-protein interactions, through a combinatorial readout of two adjacent post-translational modifications: a stable methylation and a dynamic phosphorylation mark. 相似文献
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Methylation of histone H3R2 by PRMT6 and H3K4 by an MLL complex are mutually exclusive 总被引:1,自引:0,他引:1
Guccione E Bassi C Casadio F Martinato F Cesaroni M Schuchlautz H Lüscher B Amati B 《Nature》2007,449(7164):933-937
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Peña PV Davrazou F Shi X Walter KL Verkhusha VV Gozani O Zhao R Kutateladze TG 《Nature》2006,442(7098):100-103
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Ooi SK Qiu C Bernstein E Li K Jia D Yang Z Erdjument-Bromage H Tempst P Lin SP Allis CD Cheng X Bestor TH 《Nature》2007,448(7154):714-717
Mammals use DNA methylation for the heritable silencing of retrotransposons and imprinted genes and for the inactivation of the X chromosome in females. The establishment of patterns of DNA methylation during gametogenesis depends in part on DNMT3L, an enzymatically inactive regulatory factor that is related in sequence to the DNA methyltransferases DNMT3A and DNMT3B. The main proteins that interact in vivo with the product of an epitope-tagged allele of the endogenous Dnmt3L gene were identified by mass spectrometry as DNMT3A2, DNMT3B and the four core histones. Peptide interaction assays showed that DNMT3L specifically interacts with the extreme amino terminus of histone H3; this interaction was strongly inhibited by methylation at lysine 4 of histone H3 but was insensitive to modifications at other positions. Crystallographic studies of human DNMT3L showed that the protein has a carboxy-terminal methyltransferase-like domain and an N-terminal cysteine-rich domain. Cocrystallization of DNMT3L with the tail of histone H3 revealed that the tail bound to the cysteine-rich domain of DNMT3L, and substitution of key residues in the binding site eliminated the H3 tail-DNMT3L interaction. These data indicate that DNMT3L recognizes histone H3 tails that are unmethylated at lysine 4 and induces de novo DNA methylation by recruitment or activation of DNMT3A2. 相似文献
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用Ph3SnCl与NaO2C4H3S反应,合成了Ph3SnO2C4H3S,并进行了红外光谱、核磁共振氢谱及质谱表征.X-射线单晶衍射表明,该化合物的晶体是由孤立的分子所组成,四配位的锡原子呈畸变的四面体构型,配体噻吩环上的硫原子和锡原子之间存在弱的配位作用. 相似文献
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Selective recognition of methylated lysine 9 on histone H3 by the HP1 chromo domain 总被引:108,自引:0,他引:108
Bannister AJ Zegerman P Partridge JF Miska EA Thomas JO Allshire RC Kouzarides T 《Nature》2001,410(6824):120-124
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Bird AW Yu DY Pray-Grant MG Qiu Q Harmon KE Megee PC Grant PA Smith MM Christman MF 《Nature》2002,419(6905):411-415