Differentiation-dependent chromatin alterations precede and accompany transcription of immunoglobulin light chain genes

We have studied the nature of chromatin alterations along immunoglobulin light chain (IgL) genes during B cell development using cultured murine cell lines. Employing a chromatin fractionation procedure on micrococcal nuclease-treated nuclei, we demonstrate that transcriptionally active κ IgL chromatin lacks a canonical nucleosomal repeat and exhibits a pronoduced association with insoluble nuclear material but is processed by nuclease to a soluble nucleosomal component that apparently lacks histone H1 and is enriched in high mobility group proteins. Of particular significance, utilizing a variant plasmacytoma cell line that has transcriptionally inactivated one κ allele via a promoter deletion, we demonstrate that transcription per se is not responsible for these novel alterations. Furthermore, we show that the chromatin encompassing germline (unrearranged) and transcriptionally silent λ IgL alleles in κ-producing plasmacytomas exhibit some of the same unusual properties that are displayed by κ alleles. Finally, we demonstrate that these alterations only occur in cell lines of the lymphocyte lineage that have progressed past the early pre-B cell stage; when inactive, both κ and λ IgL genes possess typical nucleosomal packaging and co-fractionate with histone H1-containing chromatin. These findings lead us to propose a model that predicts B cell stage-specific alternations in IgL chromatin prior to gene rearrangement and transcription.