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1.  Comparative gene expression profiling of placentas from patients with severe pre-eclampsia and unexplained fetal growth restriction 
Background
It has been well documented that pre-eclampsia and unexplained fetal growth restriction (FGR) have a common etiological background, but little is known about their linkage at the molecular level. The aim of this study was to further investigate the mechanisms underlying pre-eclampsia and unexplained FGR.
Methods
We analyzed differentially expressed genes in placental tissue from severe pre-eclamptic pregnancies (n = 8) and normotensive pregnancies with or (n = 8) without FGR (n = 8) using a microarray method.
Results
A subset of the FGR samples showed a high correlation coefficient overall in the microarray data from the pre-eclampsia samples. Many genes that are known to be up-regulated in pre-eclampsia are also up-regulated in FGR, including the anti-angiogenic factors, FLT1 and ENG, believed to be associated with the onset of maternal symptoms of pre-eclampsia. A total of 62 genes were found to be differentially expressed in both disorders. However, gene set enrichment analysis for these differentially expressed genes further revealed higher expression of TP53-downstream genes in pre-eclampsia compared with FGR. TP53-downstream apoptosis-related genes, such as BCL6 and BAX, were found to be significantly more up-regulated in pre-eclampsia than in FGR, although the caspases are expressed at equivalent levels.
Conclusions
Our current data indicate a common pathophysiology for FGR and pre-eclampsia, leading to an up-regulation of placental anti-angiogenic factors. However, our findings also suggest that it may possibly be the excretion of these factors into the maternal circulation through the TP53-mediated early-stage apoptosis of trophoblasts that leads to the maternal symptoms of pre-eclampsia.
doi:10.1186/1477-7827-9-107
PMCID: PMC3199758  PMID: 21810232
2.  Hbo1 Links p53-Dependent Stress Signaling to DNA Replication Licensing▿  
Molecular and Cellular Biology  2007;28(1):140-153.
Hbo1 is a histone acetyltransferase (HAT) that is required for global histone H4 acetylation, steroid-dependent transcription, and chromatin loading of MCM2-7 during DNA replication licensing. It is the catalytic subunit of protein complexes that include ING and JADE proteins, growth regulatory factors and candidate tumor suppressors. These complexes are thought to act via tumor suppressor p53, but the molecular mechanisms and links between stress signaling and chromatin, are currently unknown. Here, we show that p53 physically interacts with Hbo1 and negatively regulates its HAT activity in vitro and in cells. Two physiological stresses that stabilize p53, hyperosmotic shock and DNA replication fork arrest, also inhibit Hbo1 HAT activity in a p53-dependent manner. Hyperosmotic stress during G1 phase specifically inhibits the loading of the MCM2-7 complex, providing an example of the chromatin output of this pathway. These results reveal a direct regulatory connection between p53-responsive stress signaling and Hbo1-dependent chromatin pathways.
doi:10.1128/MCB.00662-07
PMCID: PMC2223294  PMID: 17954561
3.  A ρ-dependent termination site in the gene coding for tyrosine tRNA su3 of Escherichia coli 
Nature  1978;272(5652):423-428.
A set of partially overlapping DNA restriction fragments that support promoter-dependent transcription of the tRNA1Tyr gene of Escherichia coli has been used to study site-specific termination in vitro. Transcription termination occurs at a specific site 224–226 nucleotides beyond the end of the structural gene and is completely dependent on ρ-factor. Certain features of this site suggest differences from other termination sites previously studied. A role for specific sequence recognition is suggested.
PMCID: PMC1994828  PMID: 345126
4.  Heterogeneity in the modification and involvement of chromatin components of the CpG island of the silenced human CDH1 gene in cancer cells 
Nucleic Acids Research  2002;30(21):4770-4780.
The structural alteration of chromatin has a key role in regulating gene expression. The alteration of chromatin is mediated by modification of its components. Detailed understanding of the relationship between these modifications, notably, methylation of the full-length CpG island, the association of methyl-CpG binding proteins (MBPs), and the acetylation and methylation of histones in gene silencing is vitally important. Currently, however, the manner in which chromatin components, associated with a specific gene, are modified is poorly understood. Here we provide in vivo evidence in cancer cells of the differential association between CpG methylation, MBPs, and histone modification in the entire CpG island of the human E-cadherin (CDH1) gene. Of the cell lines with CDH1 transcriptional repression, the distribution of methyl-CpGs in the CpG island differed markedly. In a cell line with gene silencing, the promoter region was almost methylation-free. Chromatin immunoprecipitation analysis revealed that the acetylation status of histone H4 differed between cell lines. However, deacetylated histone H3 was associated with the CpG island in all silenced cell lines. Binding of MeCP2 was also detected in all silenced cell lines. Additional binding of MBD1 protein was detected in a cell line in which the promoter region was poorly methylated and only histone H3 was deacetylated. Binding of MBD2 protein was detected in all other silenced cell lines. Histone H3 lysine 9 was methylated in all silenced cells, while histone H3 lysine 4 was methylated in some silenced cell lines. These results demonstrate that chromatin components associated with inactive CDH1 chromatin is heterogeneously modified and suggests the presence of multiple pathways for the formation of inactive chromatin.
PMCID: PMC135805  PMID: 12409468
5.  Sequence of the gene for isoleucine tRNA1 and the surrounding region in a ribosomal RNA operon of Escherichia coli 
Nucleic Acids Research  1979;6(2):575-592.
A DNA fragment of about 2000 base pairs carrying the gene for tRNA1Ile has been cloned from a total Eco RI endonuclease digest of Escherichia coli DNA. Sequence analyses revealed that about the first 850 base pairs from one end of the fragment contain a nucleotide sequence corresponding to that in the 3'-end of 16S rRNA. The gene for tRNAIle follows the 16S rRNA gene and both genes flank a spacer sequence of 68 base pairs. The spacer region contains a repeating, a hair pin and a symmetrical structure when the sequence is viewed in the single stranded form. A notable hair pin structure is also observed in the region adjacent to the 3'-end of the tRNA1Ile gene. In addition, about 850 base pairs from the other end of the DNA fragment have been found to contain the nucleotide sequence of the 5'-end of 23S rRNA. The presence of the genes for tRNA1Ile, 16S and 23S rRNA and the hybridization to tRNA1Ala suggest that this cloned DNA is part of one of the E. coli rRNA operons carrying these two tRNA genes as a spacer.
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PMCID: PMC327714  PMID: 370791

Results 1-5 (5)