Transcriptional activation of Histone H1° during neuronal terminal differentiation

We have examined the central nervous system (CNS) of developing and adult transgenic mice carrying sequences upstream of the histone H1° gene fused to the E. coli β-galactosidase gene (lac Z). The transgene is induced in a subset of the neuronal population during postnatal development, coinciding with neuronal teminal differentiation. At postnatal day 9, the earliest time at which the transgene product can be detected, positive neurons are observed in the granular layer of the cerebellar cortex and in the pyramidal fields of the hippocampus. The transgene is then induced in other areas of the CNS, such as the neocortex, thalamus, hypothalamus, olfactory bulb, globus pallidus superior and inferior colliculus, substantia nigra, pontine nuclei and brain stem. Induction is unrelated with determination and quiescence, which are essentially prenatal. The overlapping of the temporal and regional patterns of transgene activity with those of the endogenous protein shows that the accumulation of H1° in differentiating neurons is at least in part under transcriptional control. In the light of these results, the H1° gene appears as the only mammalian histone gene that specifically responds to terminal differentiation. However, not all terminally differentiated neurons express H1° at detectable levels. For instance, Purkinje cells are negative. In neurons, terminal differentatiation appears thus as a necessary, but not a sufficient condition for increased H1° expression. © 1994.