J R Davie

..We propose that persistent activation of the Ras-MAPK pathway and MSK1 resulting in the elevation of phosphorylated H3 levels may contribute to the aberrant gene expression observed in the oncogene-transformed cells...

..This article will review the potential of these reversible epigenetic processes as targets for cancer therapies...

..In the cases of HDAC1 - 3, selectivity of HDAC inhibitors should be directed against relevant complexes. HDAC8 active site unique features facilitate the design of selective inhibitors...

..HDAC inhibitors might also regulate transcription elongation and have been shown to impinge on alternative splicing...

..Pending the cell background, the nonproliferating cells may enter differentiation or apoptotic pathways. The potential of butyrate and HDAC inhibitors in the prevention and treatment of cancer is presented...

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..A new and exciting development, presented in this review, is the role of signal transduction pathways in the phosphorylation of histone H3 and the expression of immediate-early genes. J. Cell. Biochem. Suppls. 32/33:141-148, 1999...

..Histone phosphorylation may lead to decondensation of chromatin, resulting in aberrant gene expression...

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..The recruited enzymes may either acetylate or deacetylate proximal nucleosomal histones or nonhistone chromosomal proteins...

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..The elevated lability of the H2A-H2B dimer may facilitate processes such as the exchange of these dimers with newly synthesized histones, the elongation process of transcription and transcription factor binding...

..Elevated levels of phosphorylated H1 and H3 may be responsible for the less condensed chromatin structure and aberrant gene expression observed in the oncogene-transformed cells...

..Phosphorylation of H1b may be required to maintain a more decondensed chromatin structure to facilitate transcription and replication processes...

..Our observations are consistent with a model in which nuclear matrix-associated histone acetyltransferases and deacetylases mediate a dynamic attachment between active and competent chromatin and the nuclear matrix...

..By affecting chromatin compaction "hi" FGF-2 may contribute to the regulation of gene expression...

..We propose that in addition to catalyzing dynamic acetylation of transcribed chromatin, the enzyme has a role in the organization of nuclear DNA...

..These results show that although both stimuli lead to TFF1 gene activation, estradiol and TPA exert their effects on TFF1 gene expression by different mechanisms...

..However, the in vivo data are somewhat contradictory and limited by the small cohorts used and the lack of standard well-characterized reagents and protocols...

..Our results suggest that progression of breast cancer is accompanied by a reorganization of chromosomal domains, which may lead to alterations in gene expression...

..We speculate that its ubiquitination could loosen the nucleosome structure in preparation for histone removal, be a consequence of nucleosome relaxation or disruption caused by other means, or target H3 for degradation...

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..The sex hormone estrogen (E2) is pivotal to normal mammary gland growth and differentiation and in breast carcinogenesis. In this in silico study, we examined metabolic differences between ER(+)ve breast cancer cells during E2 deprivation...

..We conclude that in cultured T5 breast cancer cells H3 and H4 are in highly acetylated states maintaining the unfolded structure of the transcribed nucleosome and facilitating subsequent rounds of elongation...

..Our results present evidence that nonclonal chromosomal aberrations and epigenetic programming responding to stimulation of the Ras-MAPK pathway may be better markers for cancer progression than the upstream mutated oncogenes...

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..The recruited SWI/SNF remodels nucleosomes at the promoter of IE genes enabling the binding of transcription factors like JUN and the onset of transcription...

..Although Sp1/Sp3 is not involved in the recruitment of ER alpha to the promoter, Sp1 is necessary for estrogen-induced p21(Waf1/Cip1) promoter activity...

..Furthermore, GFP-ER expression did not affect the estradiol induced temporal expression of hormone responsive genes c-myc and pS2...

..CK2 phosphorylation of HDAC2 recruited by Sp1 or Sp3 could regulate HDAC activity and alter the balance of histone deacetylase and histone acetyltransferase activities and dynamic chromatin remodeling of estrogen-regulated genes...

..The chromatin remodelling actions of these modified histones may result in aberrant gene expression...

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..These observations are consistent with the hypothesis that ubiquitinated histones have a role maintaining the structure of transcriptionally active chromatin...

..These models are relevant and will be useful for dissecting the role of ERbeta1 expression in ER-positive breast cancer...

..Thus, repressor complexes such as Sin3, appear to be stable in the presence of TSA. The association of HDAC2 with transcription factor Sp1 is also not affected by TSA...

..In this article, we present the ChIP assay currently used in our lab and discuss the various ways to optimize this assay for one's own use...

..Procedures to assay the activities of these enzymes and to measure the kinetics of histone acetylation and deacetylation are presented...

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..The similarity of the repeat pattern in trout and human apoA-Is suggests that all the internal repeats in these sequences arose before the fish-mammal split, some 400 million years ago...

..The cellular contexts under which specific residues on H3 are phosphorylated in mitosis and interphase are known to some extent. However, the functional consequences of H3 phosphorylation are still unclear...

..Together our results demonstrate the increased genomic instability and alterations in the epigenetic program in HRAS-transformed cells...

..For example, recent studies challenge the idea that DNA methylation is irreversible. Further, research on Rett syndrome has revealed an unforeseen role for methyl-CpG-binding protein 2 (MeCP2) in neurons...

..3 phosphorylated at serine 28 was present in labile nucleosomes. We propose that destabilized nucleosomes containing H3.3 phosphorylated at serine 28 aid in the dynamic disassembly-assembly of nucleosomes in active promoters...

..Taken together, these results provide evidence that Sp3 and ERalpha are involved in the estrogen induced transcription of the TFF1 gene...

..These studies suggest a novel role for TG2 in the regulation of chromatin structure and function...

..The results show that elevated levels of ER prevented the down-regulation of p21 protein expression, which is required for hormone responsive cells to enter S phase...

..Regulation of the transcriptional activity of Sp1 and Sp3 occurs largely at the post-translational level. In this review, we focus on the roles of Sp1 and Sp3 in the regulation of gene expression...

..These data support the hypothesis that psoriasin/S100A7 is specifically regulated by ERbeta activity and could be useful to guide future therapies targeting ERbeta in certain phenotypic subsets of breast cancers in-vivo...

..We provide evidence that unmodified HDAC2 is associated with the coding region of transcribed genes, whereas phosphorylated HDAC2 is primarily recruited to promoters...

..The resulting levels of estrogen receptor and the type of ligand bound to it have a direct impact on the transcription of estrogen-responsive genes...

..We propose that CTCF may demarcate nuclear matrix-dependent points of transition in chromatin, thereby forming topologically independent chromatin loops that may support gene silencing...

..In this review, the role of Sp1 and Sp3 in normal and cancer cell biology and the multiple mechanisms deciding the functional roles of Sp1 and Sp3 will be presented...

..Our results demonstrate the different features of Sp1 and Sp3, providing further evidence that Sp3 is not a functional equivalent of Sp1...

..Both Sp1 and Sp3 return to the nuclei ahead of RNA polymerase II. Our results support a model in which entry of Sp1, Sp3 and RNA polymerase II into the newly formed nuclei is an ordered process...

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..The elucidation of how the memory of a programmed expression profile is transmitted to daughter cells represents a challenge...

..This article will review genetic and epigenetic events that alter chromatin organization in cancer cells and the role of the nuclear matrix in determining nuclear morphology...

..In vitro, butyrate inhibits histone deacetylase and down-regulates expression of cyclin D1. We hypothesized that an increased entry rate of butyrate into the cecal lumen would have similar effects in vivo...

..They also suggest that NF-E2 may function both positively and negatively in the transcription regulation of specific erythroid and megakaryocytic genes...

..These studies provide further insight into the molecular mechanisms underlying the heterogeneity of DPD activity, and may facilitate the efficacy and safety of 5-FU-based chemotherapy...

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..This may also provide insight into the mechanism underlying the downregulation of DPYD in some colorectal cancers...

..Splicing assays show that CHD1 overexpression can affect alternative splicing. These results suggest that CHD1 may function in both chromatin mediated transcriptional repression and RNA splicing...