1: Toxicol Appl Pharmacol. 2004 Apr 1;196(1):37-46. 

Exposure of Tg.AC transgenic mice to benzene suppresses hematopoietic progenitor
cells and alters gene expression in critical signaling pathways.

Nwosu VC, Kissling GE, Trempus CS, Honeycutt H, French JE.

Department of Biology, North Carolina Central University, Durham, NC 27707, USA.
vcnwosu@wpo.nccu.edu

The effects of acute benzene (BZ) exposure on hematopoietic progenitor cells
(HPCs) derived from bone marrow cells were studied using homozygous male
v-Ha-ras Tg.AC mice at 8-10 weeks of age. The mice were given 0.02% BZ in their
drinking water for 28 days with the dose rate estimated to be 34 mg benzene/kg
BW/day. Analysis of cultured HPCs indicated that BZ suppressed the proliferation
of the multilineage colony forming unit-granulocyte, erythrocyte, macrophage,
megakaryocyte (CFU-GEMM); colony forming unit-granulocyte, macrophage (CFU-GM);
and blast forming unit erythrocyte/colony forming unit erythrocyte (BFUE/CFUE).
A gene expression profile was generated using nylon arrays spotted with 23 cDNAs
involved in selected signal pathways involved in cell distress, inflammation,
DNA damage, cell cycle arrest, and apoptosis. Of the 23 marker genes, 6 (bax,
c-fos, E124, hsf1, ikBa, and p57) were significantly (Mann-Whitney U tests, P <
0.05) overexpressed in BZ-exposed mice. Two genes (c-myc and IL-2) approached
significance (at P = 0.053). The pattern of gene expression was consistent with
BZ toxicity and the suppression of HPCs.

PMID: 15050406 [PubMed - indexed for MEDLINE]


---------------------------------------------------------------


2: Genes Dev. 1996 Jun 15;10(12):1479-90. 

Activator-dependent regulation of transcriptional pausing on nucleosomal
templates.

Brown SA, Imbalzano AN, Kingston RE.

Department of Genetics, Harvard Medical School, Boston, Massachusetts 02114,
USA.

Promoter-proximal pausing during transcriptional elongation is an important way
of regulating many diverse genes, including human c-myc and c-fos, some HIV
genes, and the Drosophila heat shock loci. To characterize the mechanisms that
regulate pausing, we have established an in vitro system using the human hsp7O
gene. We demonstrate that nucleosome formation increases by >100-fold the
duration of a transcriptional pause on the human hsp7O gene in vitro at the same
location as pausing is observed in vivo. Readthrough of this pause is increased
by an activator that contains the human heat shock factor 1 (HSF1)
transcriptional activation domains. Maximal effect of the activator requires
that the system be supplemented with fractions that have hSWI/SNF activity,
which has been shown previously to alter nucleosome structure. No significant
readthrough is observed in the absence of activator, and neither the activator
nor the hSWI/SNF fraction affected elongation on naked DNA; therefore, these
results suggest that an activator can cause increased readthrough of
promoter-proximal pausing by decreasing the inhibitory effect of nucleosomes on
transcriptional elongation.

PMID: 8666232 [PubMed - indexed for MEDLINE]


---------------------------------------------------------------