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依赖ATP的染色质物理修饰 总被引：2，自引：0，他引：2
染色质重塑是基因表达调控过程中一个非常重要的环节 .染色质重塑主要包括 2种类型 :一种是依赖ATP的物理修饰 ,另一种是依赖共价结合反应的化学修饰 .依赖ATP的物理修饰主要是利用ATP水解释放的能量 ,使DNA超螺旋旋矩和旋相发生变化 ,使转录因子更易接近并结合核小体DNA ,从而调控基因的转录过程 相似文献
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真核细胞中的染色质重塑因子种类繁多,多数以蛋白多聚体的形式存在于细胞中．不同的染色质重塑因子在特定时间定位于特定的核小体上,通过改变染色质结构,影响基因转录活性,进而确保细胞内各种生物学过程的正确运行．另外,染色质重塑因子根据所含功能结构域的不同,大致分为SWI/SNF、ISWI、CHD和INO80四大家族,不同的染色质重塑因子之间既有蛋白质结构和酶活性的相似性,各自又有其特异性．本综述的宗旨在于全面概括和总结染色质重塑因子的分类、结构特点以及其在细胞内的生物学功能,为深入研究染色质重塑因子的生物学功能,尤其是在发育和疾病发生中的作用机制提供理论基础． 相似文献
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Pluripotent embryonic stem cells (ESCs) are characterized by distinct epigenetic features including a relative enrichment of histone modifications related to active chromatin. Among these is tri‐methylation of lysine 4 on histone H3 (H3K4me3). Several thousands of the H3K4me3‐enriched promoters in pluripotent cells also contain a repressive histone mark, namely H3K27me3, a situation referred to as “bivalency”. While bivalent promoters are not unique to pluripotent cells, they are relatively enriched in these cell types, largely marking developmental and lineage‐specific genes which are silent but poised for immediate action. The H3K4me3 and H3K27me3 modifications are catalyzed by lysine methyltransferases which are usually found within, although not entirely limited to, the Trithorax group (TrxG) and Polycomb group (PcG) protein complexes, respectively, but these do not provide selective bivalent specificity. Recent studies highlight the family of ATP‐dependent chromatin remodeling proteins as regulators of bivalent domains. Here, we discuss bivalency in general, describe the machineries that catalyze bivalent chromatin domains, and portray the emerging connection between bivalency and the action of different families of chromatin remodelers, namely INO80, esBAF, and NuRD, in pluripotent cells. We posit that chromatin remodeling proteins may enable “bivalent specificity”, often selectively acting on, or selectively depleted from, bivalent domains. 相似文献
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真核细胞中,基因组DNA缠绕组蛋白八聚体形成核小体,核小体再经过多层次折叠压缩形成具有高级结构的染色质．过去30多年,科学家对30 nm染色质纤维的结构进行了大量的研究,然而关于30 nm染色质纤维的精细结构仍然存在很大的争议．本文综述了近年来对30 nm染色质纤维结构的最新研究进展,并重点阐述了最近解析的30 nm染色质纤维左 手双螺旋结构．同时,我们还进一步讨论了一些对30 nm染色质纤维结构起调控作用的因子及其作用机制．最后,我们对30 nm染色质纤维结构与功能领域所面临的挑战和问题进行了展望． 相似文献
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Suto RK Edayathumangalam RS White CL Melander C Gottesfeld JM Dervan PB Luger K 《Journal of molecular biology》2003,326(2):371-380
We determined the crystal structures of three nucleosome core particles in complex with site-specific DNA-binding ligands, the pyrrole-imidazole polyamides. While the structure of the histone octamer and its interaction with the DNA remain unaffected by ligand binding, nucleosomal DNA undergoes significant structural changes at the ligand-binding sites and in adjacent regions to accommodate the ligands. Our findings suggest that twist diffusion occurs over long distances through tightly bound nucleosomal DNA. This may be relevant to the mechanism of ATP-dependent and spontaneous nucleosome translocation, and to the effect of bound factors on nucleosome dynamics. 相似文献
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染色质高度紧密的折叠阻止了转录因子和辅因子与DNA的结合, 因而通过染色质重塑以解除这样的抑制环境, 对于转录活动的正常进行是至关重要的。目前认为, 染色质重塑至少是通过两种机制来完成的, 一种是通过ATP依赖的染色质改构复合物, 另一种是通过对组蛋白尾部进行共价修饰的组蛋白修饰酶复合物。文章结合近年来的研究进展, 对前者进行染色质重塑的机制及两者在基因转录调控过程中如何相互协作等进行了论述。 相似文献
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Lois R. Manning James M. Manning 《Protein science : a publication of the Protein Society》2018,27(3):662-671
The effect of phosphorylation on the basicities of amines in histone H3 peptides and their acetylation kinetics is probed with a mild chemical acetylating agent. Phosphorylation of Ser‐10 lowers the rate of chemical acetylation of Lys‐9, Lys‐14, and Lys‐18 by methyl acetyl phosphate in that order consistent with a higher pKa of these Lys residues induced by phosphorylation; basicities increase up to 3 pKa units as a function of distance from Ser‐10 phosphate. Enzymic acetylation of Lys residues with high pKa values in nucleosomes is also expected to be enhanced by phosphorylation, consistent with the known mechanism involving binding of protonated amines to N‐acetyltransferases; fetal hemoglobin has a related linkage of increased basicity at a specific site, its acetylation, and a resulting decrease in subunit interaction strength. In the absence of a phosphate on Ser‐10, the amines of Lys‐9, Lys‐14, and Lys‐18 have lowered pKa values. Chemical acetylation of glycine and glycinamide have analogous kinetic profiles to the histone peptides but the phosphate inductive effect in histone H3 is more potent since the linkage between phosphorylation and acetylation is propagated with a range extending 9–10 amino acids in either direction from the phosphorylation site enhancing protonation of amino groups. We conclude that lysine amine basicities in histone tails are not static but inducible and variable due to a dynamic and immediate interaction between phosphorylation/acetylation that may contribute to inactive heterochromatin by compaction through such Ser phosphate–Lys amine electrostatic interactions and their relaxation by acetylation in euchromatin. 相似文献
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Hideaki Niwa Noriko Handa Yuri Tomabechi Keiko Honda Mitsutoshi Toyama Noboru Ohsawa Mikako Shirouzu Hiroyuki Kagechika Tomoya Hirano Takashi Umehara Shigeyuki Yokoyama 《Acta Crystallographica. Section D, Structural Biology》2013,69(4):595-602
SET7/9 is a protein lysine methyltransferase that methylates histone H3 and nonhistone proteins such as p53, TAF10 and oestrogen receptor α. In previous work, novel inhibitors of SET7/9 that are amine analogues of the coenzyme S‐(5′‐adenosyl)‐L‐methionine (AdoMet) have been developed. Here, crystal structures of SET7/9 are reported in complexes with two AdoMet analogues, designated DAAM‐3 and AAM‐1, in which an n‐hexylaminoethyl group or an n‐hexyl group is attached to the N atom that replaces the S atom of AdoMet, respectively. In both structures, the inhibitors bind to the coenzyme‐binding site and their additional alkyl chain binds in the lysine‐access channel. The N atom in the azaalkyl chain of DAAM‐3 is located at almost the same position as the N‐methyl C atom of the methylated lysine side chain in the substrate–peptide complex structures and stabilizes complex formation by hydrogen bonding to the substrate‐binding site residues of SET7/9. On the other hand, the alkyl chain of AAM‐1, which is a weaker inhibitor than DAAM‐3, binds in the lysine‐access channel only through hydrophobic and van der Waals interactions. Unexpectedly, the substrate‐binding site of SET7/9 complexed with AAM‐1 specifically interacts with the artificial N‐terminal sequence of an adjacent symmetry‐related molecule, presumably stabilizing the alkyl chain of AAM‐1. 相似文献
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Histone proteins dynamically regulate chromatin structure and epigenetic signaling to maintain cell homeostasis. These processes require controlled spatial and temporal deposition and eviction of histones by their dedicated chaperones. With the evolution of histone variants, a network of functionally specific histone chaperones has emerged. Molecular details of the determinants of chaperone specificity for different histone variants are only slowly being resolved. A complete understanding of these processes is essential to shed light on the genuine biological roles of histone variants, their chaperones, and their impact on chromatin dynamics. 相似文献
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Histone modifications not only play important roles in regulating chromatin structure and nuclear processes but also can be passed to daughter cells as epigenetic marks. Accumulating evidence suggests that the key function of histone modifications is to signal for recruitment or activity of downstream effectors. Here, we discuss the latest discovery of histone-modification readers and how the modification language is interpreted. 相似文献