Biomedical subjects

E H Raabe

Publications and source records attributed to E H Raabe.

3 recordsLinked to original sources

PubMed2001

An SNF2 factor involved in mammalian development and cellular proliferation.

Members of the SNF2 (Sucrose Non-Fermenter) family of chromatin-remodeling proteins function in processes ranging from DNA repair to transcription to methylation. Using differential display, we recently identified a novel member of the SNF2 family that is highly expressed at the mRNA level in proliferating cells and is down-regulated during apoptosis. We have named this gene PASG (Proliferation-Associated SNF2-like Gene). Northern blot analysis of adult mouse tissues shows PASG to be highly expressed in proliferating organs such as thymus, bone marrow, and testis and absent from nonproliferative tissues such as brain and heart. In situ hybridization analysis of mouse embryos shows that PASG is differentially expressed during development, with highest expression in developing face, limbs, skeletal muscle, heart, and tail. In vitro, PASG expression correlates with a shift from a quiescent to a proliferative state. Mice null for PASG (also known as LSH or Hells) are reported to die perinatally, although the mechanism for lethality is unclear (Geiman and Muegge, 2000). To test the hypothesis that PASG functions in cell proliferation, we compared 5-bromodeoxyuridine (BrdU) incorporation in C33A cells transiently transfected with PASG versus empty vector and found that PASG transfected cells showed a significant decrease in the amount of BrdU incorporation. These findings suggest that PASG plays a role in cell proliferation and may function in the development of multiple cell lineages during murine embryogenesis.

3T3 Cells↗

PubMed2000

Proliferation-associated SNF2-like gene (PASG): a SNF2 family member altered in leukemia.

To identify genes involved in cell growth and/or apoptosis in leukemia, differential display was used to identify mRNAs that showed altered expression levels after cytokine withdrawal from the cytokine-dependent MO7e cell line. Sequence analysis of one transcript that showed a profound decrease in expression after cytokine withdrawal revealed it to be a member of the SNF2 family of chromatin remodeling ATPases. This cDNA had a 2514-nucleotide (838-amino acid) open reading frame and encoded an additional 230 amino acids at the NH2 terminus compared with the murine homologue, lsh, and the human counterpart, Hells. This gene locus has been designated SMARCA6 (SWI/SNF2-related, matrix-associated, actin-dependent regulator of chromatin, subfamily A, member 6). The highest levels of mRNA expression in humans are observed in proliferative tissues such as the thymus, testis, and bone marrow. Whereas cytokine withdrawal in MO7e cells leads to apoptosis and decreased mRNA expression, growth arrest without the induction of apoptosis of MO7e cells also leads to down-regulation of mRNA expression, suggesting an association with cell proliferation and not suppression of apoptosis. Nuclear localization of this SNF2-like putative helicase is dependent on a nuclear localization sequence located in the NH2-terminal region. Based on sequence homology to other SNF2-like helicases, the pattern of tissue expression, and the association of expression with cell proliferation, we refer to the protein product as proliferation-associated SNF2-like gene product [PASG (D. W. Lee et al., Blood, 94: 594a, 1999)]. Examination of acute myelogenous leukemia and acute lymphoblastic leukemia samples revealed a high frequency of a PASG transcript containing an in-frame 75-nucleotide deletion, which codes for a conserved motif known to be critical for the transactivation activity of a related yeast SWI/SNF polypeptide. These results extend our knowledge of this SNF2-like family member and suggest a role for PASG in leukemogenesis.

Alternative Splicing↗

PubMed1997

Differential laminin isoform expression in the developing rat olfactory system.

Members of the laminin family influence mammalian cells in a variety of ways, mediating adhesion, proliferation, migration, and growth of neuronal processes. Specific laminin domains act through a number of cellular interaction sites to mediate these activities. In the developing olfactory system, axons grow from the olfactory epithelium to synaptic sites in the olfactory bulb a matrix rich in laminins and known mediators of laminin-axon interactions include integrins and a galectin-1/glycoconjugate adhesion system. Using biochemistry, immunocytochemistry, and in situ hybridization, we identified alpha 2, alpha 3, beta 1, beta 2 and gamma 1 laminin isoforms in the late embryonic and neonatal rat olfactory system. However, alpha 1-containing laminin could not be detected in association with olfactory neurons. Immunocytochemistry revealed that beta 2 laminin is preferentially expressed in the ventral and lateral nerve layer of the olfactory bulb and in the main olfactory axon tracks, but is undetectable in the accessory system during embryonic and early postnatal development. In contrast, beta 1 and gamma 1 laminins are evenly distributed throughout the olfactory bulb and in both the main and accessory olfactory axon tracks. The differential localization of laminin chains in vivo is likely to have functional significance for the development and maintenance of the olfactory system.

Animals↗