共查询到20条相似文献,搜索用时 15 毫秒
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DNA methylation and the regulation of gene transcription 总被引:28,自引:0,他引:28
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Dorman CJ 《Science progress》2006,89(PT 3-4):151-166
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Vanesa Lafarga Olga Tapia Sahil Sharma Rocio Bengoechea Georg Stoecklin Miguel Lafarga Maria T. Berciano 《Cellular and molecular life sciences : CMLS》2018,75(3):527-546
The survival of motor neuron (SMN) protein plays an essential role in the biogenesis of spliceosomal snRNPs and the molecular assembly of Cajal bodies (CBs). Deletion of or mutations in the SMN1 gene cause spinal muscular atrophy (SMA) with degeneration and loss of motor neurons. Reduced SMN levels in SMA lead to deficient snRNP biogenesis with consequent splicing pathology. Here, we demonstrate that SMN is a novel and specific target of the acetyltransferase CBP (CREB-binding protein). Furthermore, we identify lysine (K) 119 as the main acetylation site in SMN. Importantly, SMN acetylation enhances its cytoplasmic localization, causes depletion of CBs, and reduces the accumulation of snRNPs in nuclear speckles. In contrast, the acetylation-deficient SMNK119R mutant promotes formation of CBs and a novel category of promyelocytic leukemia (PML) bodies enriched in this protein. Acetylation increases the half-life of SMN protein, reduces its cytoplasmic diffusion rate and modifies its interactome. Hence, SMN acetylation leads to its dysfunction, which explains the ineffectiveness of HDAC (histone deacetylases) inhibitors in SMA therapy despite their potential to increase SMN levels. 相似文献
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DNA damage repair and transcription 总被引:2,自引:0,他引:2
Berardi P Russell M El-Osta A Riabowol K 《Cellular and molecular life sciences : CMLS》2004,61(17):2173-2180
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Poly-ADP-ribosylation in health and disease 总被引:6,自引:0,他引:6
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The evolutionary conservation of eukaryotic gene transcription 总被引:1,自引:0,他引:1
M Schena 《Experientia》1989,45(10):972-983
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Protein deacetylation by sirtuins: delineating a post-translational regulatory program responsive to nutrient and redox stressors 总被引:1,自引:1,他引:0
Lysine acetylation/deacetylation is increasingly being recognized as common post-translational modification that appears to
be broadly operational throughout the cell. The functional roles of these modifications, outside of the nucleus, have not
been extensively studied. Moreover, as acetyl-CoA donates the acetyl group for acetylation, nutrient availability and energetic
status may be pivotal in this modification. Similarly, nutrient limitation is associated with the deacetylation reaction.
This modification is orchestrated by a novel family of sirtuin deacetylases that function in a nutrient and redox dependent
manner and targets non-histone protein deacetylation. In compartment-specific locations, candidate target proteins undergoing
lysine-residue deacetylation are being identified. Through these investigations, the functional role of this post-translational
modification is being delineated. We review the sirtuin family proteins, discuss their functional effects on target proteins,
and postulate on potential biological programs and disease processes that may be modified by sirtuin-mediated deacetylation
of target proteins. 相似文献
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Emerging connections between DNA methylation and histone acetylation 总被引:18,自引:0,他引:18
Modifications of both DNA and chromatin can affect gene expression and lead to gene silencing. Evidence of links between
DNA methylation and histone hypoacetylation is accumulating. Several proteins that specifically bind to methylated DNA are
associated with complexes that include histone deacetylases (HDACs). In addition, DNA methyltransferases of mammals appear
to interact with HDACs. Experiments with animal cells have shown that HDACs are responsible for part of the repressive effect
of DNA methylation. Evidence was found in Neurospora that protein acetylation can in some cases affect DNA methylation. The available data suggest that the roles of DNA methylation
and histone hypoacetylation, and their relationship with each other, can vary, even within an organism. Some open questions
in this emerging field that should be answered in the near future are discussed. 相似文献
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