http://repub.eur.nl/res/aut/425/ List of Publications en http://repub.eur.nl/static-eur/img/logo.png http://repub.eur.nl http://repub.eur.nl/res/pub/2487/ 1993-01-01T00:00:00Z We have carried out a structural and functional analysis on the human NF-L (H-NF-L) gene. It contains a methylation-free island, spanning the 5' flanking sequences and the first exon and a number of neuronal-specific DNase I hypersensitive sites have been identified in the upstream region as well as within the body of the gene. Analysis in cell lines and transgenic mice using a combination of these sites has revealed the presence of a conserved element(s) between -300bp and -190bp which is required for neuronal-specific expression. http://repub.eur.nl/res/pub/2470/ 1991-01-01T00:00:00Z http://repub.eur.nl/res/pub/2459/ 1990-01-01T00:00:00Z We used mouse embryonic stem (ES) cells to study globin gene expression and switching in vitro. We show that ES-derived embryoid bodies express the full complement of mouse embryonic globin genes in the correct temporal order and that on further differentiation, a switch occurs to the fetal/adult genes. In addition, the erythroid-specific transcription factor NF-E1 was shown to be expressed coordinately with that of globin in embryoid bodies. We conclude from these experiments that the ES cell system provides a good model to study hematopoietic development. When the human epsilon- or beta-globin genes driven by the dominant control region (DCR) are introduced into this system, the human epsilon-globin gene, in contrast to the beta-globin gene, is not deregulated by the presence of the DCR and is expressed strictly as an embryonic gene. We conclude from this that the epsilon-globin gene is not regulated by competition with other genes in the human beta-globin locus. http://repub.eur.nl/res/pub/2428/ 1988-01-01T00:00:00Z Nerve growth factor (NGF) is known to increase the levels of neurofilament proteins in PC-12 pheochromocytoma cells. In this report, we show that the three neurofilament subunits, NF-L, NF-M, and NF-H, are not induced coordinately. NF-H accumulated only after longer term NGF treatment than required for NF-L and NF-M. While NGF treatment resulted in 12- and 14-fold increases in NF-L and NF-M mRNA levels, respectively, over a 14-day period, no increase in the level of NF-H mRNA was observed. This indicated that in PC-12 cells, control of NF-H expression by NGF may occur at the post-transcriptional level. NGF appeared to have no effect on the stability of NF-L mRNA, although it increased the stability of NF-M mRNA relative to that in control PC-12 cells. Analysis of the effect of NGF on the transcription of neurofilament genes showed 4- and 5-fold increases in the rates of NF-L and NF-M gene transcription, respectively, and no increase in the rate of NF-H gene transcription. Taken together these results demonstrate that NGF stimulates the expression of individual neurofilament subunits at the transcriptional and/or post-transcriptional levels.