H1º is a member of the H1 histone family that is involved in the induction and stabilization of chromatin higher order structure. We have previosuly shown that H1º is transcriptionally activated during neuronal terminal differentiation. We have also shown that H1º is negatively regulated both by estradiol in the arcuate area and osmotic stimulation in the supraoptic nucleus. In contrast, in transfected cells thyroid hormone is necessary for sustained transcription. We will try to obtain physiological evidence in favor in the involvement of thyroid hormone in the expression of H1º in the CNS using hypothyroid transgenic mice. We will examine the regulatory elements mediating hormone regulation using techniques of transient expression, band-shift electrophoresis and footprinting. We will also analyze the pattern of transcriptional activation through the cerebral cortex layers during postnatal developement. The combination of promotor elements linking H1º expression with terminal differentiation may have coevoluted with functional differentiation in the H1 family. We will examine the affinity of H1º for different DNA sequences, including the SARs. We will also study the secondary structure of peptides of the C-terminal domain containing PKKA motifs, which are characteristic of H1º.
|Effective start/end date||1/11/96 → 1/11/99|
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