Christine E Boumah

Robert Wood Johnson University Hospital, New Brunswick, New Jersey, United States

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Publications (5)44.84 Total impact

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    ABSTRACT: PTH regulates transcription of a number of genes involved in bone remodeling and calcium homeostasis. We have previously shown that the matrix metalloproteinase-13 (MMP-13) gene is induced by PTH in osteoblastic cells as a secondary response through the protein kinase A pathway requiring the runt domain and activator protein 1 binding sites of the proximal promoter. Here, we investigated the changes PTH causes in histone acetylation in this region (which contains the only deoxyribonuclease-hypersensitive sites in the promoter) leading to MMP-13 gene activation in these cells. Chromatin immunoprecipitation experiments revealed that PTH rapidly increased histone H4 acetylation followed by histone H3 acetylation associated with the different regions of the MMP-13 proximal promoter. The hormone also stimulated p300 histone acetyl transferase activity and increased p300 bound to the MMP-13 proximal promoter, and this required protein synthesis. Upon PTH treatment, Runx2, already bound to the runt domain site of the MMP-13 promoter, interacted with p300, which then acetylated histones H4 and H3. The knockdown of either Runx2 or p300 by RNA interference reduced PTH-induced acetylation of histones H3 and H4, association of p300 with the MMP-13 promoter, and resultant MMP-13 gene transcription. Overall, our studies suggest that without altering the gross chromatin structure, PTH stimulates acetylation of histones H3 and H4 via recruitment of p300 to Runx2 bound to the MMP-13 promoter, resulting in gene activation. This work establishes the molecular basis of transcriptional regulation in osteoblasts by PTH, a hormone acting through a G-protein coupled receptor.
    Molecular Endocrinology 06/2009; 23(8):1255-63. DOI:10.1210/me.2008-0217 · 4.20 Impact Factor
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    ABSTRACT: Papillon-Lefèvre syndrome is an autosomal recessive disorder characterized by palmoplantar hyperkeratosis and aggressive periodontitis. The aim of the study was to identify underlying cathepsin C mutations in 39 subjects with Papillon-Lefèvre syndrome and to explore any phenotypic associations. Genotyping and mutation analyses were performed using standard molecular techniques, and dermatological and oral characteristics were assessed with a semiquantitative clinical score. Three genotypes were present at microsatellite marker D11S1780 and two underlying mutations were identified. The most common genotype (183/183) was associated with an 815G --> C mutation in exon 6 resulting in an arginine to proline change at amino acid 272 (R272P). Patients with the 173/173 genotype revealed an exon 7 G300D mutation resulting in a glycine to aspartic acid change at amino acid 300. The mutation in a family with 189/189 genotype remained unknown. A significant difference in hyperkeratosis of the feet was found between the patients with mutations G300D and R272P ( p < 0.05), but not regarding hands or periodontal condition. Young girls displayed significantly less palmoplantar hyperkeratosis ( p < 0.05) than young boys. In conclusion, considerable phenotypic heterogeneity was observed within the two cardinal mutations and in the 189/189 genotype.
    Acta Dermato Venereologica 02/2006; 86(1):3-7. DOI:10.1080/00015550510011619 · 4.24 Impact Factor
  • Progress in Nucleic Acid Research and Molecular Biology 02/2005; 80:287-321. DOI:10.1016/S0079-6603(05)80007-8 · 4.14 Impact Factor
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    ABSTRACT: Molecular monitoring of donor/recipient T-cell kinetics early post-transplant can provide clues to the immunological events that govern host-versus-graft reaction (HVGR) and graft versus-host-disease (GVHD). We have previously used fluorescence in situ hybridization (FISH) with X and Y probes to monitor recipient T (R-T) cell clearance early after myeloablative allogeneic stem cell transplantation (ASCT). We demonstrated that impaired clearance of residual host-T-cells in the early days post-transplant was associated with graft rejection, while enhanced clearance could be an indicator of increased donor anti-host alloreactivity and predictive of acute GVHD. Although FISH is the most accurate quantitative molecular tool for the determination of the exact donor/recipient-T-cell numbers at any time points post-transplant, it has the disadvantage of being limited to sex mismatched donor/recipient pairs. Our goal was to develop a molecular approach that, irrespective of gender, would be comparable to FISH in accurately determining host residual T-cell clearance after myeloablative conditioning for ASCT. We have genotyped DNA from cell lysates using polymerase chain reaction (PCR) amplification of short tandem repeats (STR) with fluorescently labeled oligonucleotide primers, and used the Genescan 672 software for accurate quantitative analysis of the amplified alleles. Here, we show that this approach allowed us to achieve in T-cells accurate quantitative analyses of amplified donor/recipient alleles in sex matched patients on days +5, +8 and +12 post-transplant, despite severe leukopenia.
    Leukemia and Lymphoma 07/2002; 43(6):1281-7. DOI:10.1080/10428190290026349 · 2.61 Impact Factor
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    ABSTRACT: The inherited osteolyses or 'vanishing bone' syndromes are a group of rare disorders of unknown etiology characterized by destruction and resorption of affected bones. The multicentric osteolyses are notable for interphalangeal joint erosions that mimic severe juvenile rheumatoid arthritis (OMIMs 166300, 259600, 259610 and 277950). We recently described an autosomal recessive form of multicentric osteolysis with carpal and tarsal resorption, crippling arthritic changes, marked osteoporosis, palmar and plantar subcutaneous nodules and distinctive facies in a number of consanguineous Saudi Arabian families1, 2. We localized the disease gene to 16q12−21 by using members of these families for a genome-wide search for homozygous-by-descent microsatellite markers. Haplotype analysis narrowed the critical region to a 1.2-cM region that spans the gene encoding MMP-2 (gelatinase A, collagenase type IV; (ref. 3). We detected no MMP2 enzymatic activity in the serum or fibroblasts of affected family members. We identified two family-specific homoallelic MMP2 mutations: R101H and Y244X. The nonsense mutation effects a deletion of the substrate-binding and catalytic sites and the fibronectin type II-like and hemopexin/TIMP2 binding domains. Based on molecular modeling, the missense mutation disrupts hydrogen bond formation within the highly conserved prodomain adjacent to the catalytic zinc ion.
    Nature Genetics 06/2001; 28(3):261-265. DOI:10.1038/90100 · 29.65 Impact Factor

Publication Stats

175 Citations
44.84 Total Impact Points


  • 2005
    • Robert Wood Johnson University Hospital
      New Brunswick, New Jersey, United States
  • 2002
    • King Faisal Specialist Hospital and Research Centre
      Ar Riyāḑ, Ar Riyāḑ, Saudi Arabia