Hormone-mediated dephosphorylation of specific histone H1 isoforms

We have previously shown a connection between histone H1 phosphorylation an d the transcriptional competence of the hormone inducible mouse mammary tum or virus (MMTV) promoter. Prolonged exposure of mouse cells to dexamethason e concurrently dephosphorylated histone H1 and rendered the MMTV promoter r efractory to hormonal stimulation and, therefore, transcriptionally unrespo nsive. Using electrospray mass spectrometry, we demonstrate here that prolo nged dexamethasone treatment differentially effects a subset of the six som atic H1 isoforms in mouse cells. H1 isoforms H1.0, H1.1, and H1.2 are non-r esponsive to hormone whereas prolonged dexamethasone treatment effectively dephosphorylated the H1.3, H1.4, and H1.5 isoforms. The protein kinase inhi bitor staurosporine, shown to dephosphorylate historic H1 and down-regulate MMTV in cultured cells, appears only to completely dephosphorylate the H1. 3 isoform. These results suggest that dephosphorylation of specific histone H1 isoforms may contribute to the previously observed decrease in transcri ptional competence of the MMTV promoter through the modulation of chromatin structure. In a broader sense, this work advances the hypothesis that post -translational modifications of individual histone H1 isoforms directly inf luence the transcriptional activation/repression of specific genes.