Abstract
BackgroundThere are 11 variants of linker histone H1 in mammalian cells. Beyond their shared abilities to stabilize and condense chromatin, the H1 variants have been found to have non-redundant functions, the mechanisms of which are not fully understood. Like core histones, there are both replication-dependent and replication-independent linker histone variants. The histone chaperones and other factors that regulate linker histone dynamics in the cell are largely unknown. In particular, it is not known whether replication-dependent and replication-independent linker histones interact with distinct or common sets of proteins. To better understand linker histone dynamics and assembly, we used chromatography and mass spectrometry approaches to identify proteins that are associated with replication-dependent and replication-independent H1 variants. We then used a variety of in vivo analyses to validate the functional relevance of identified interactions.ResultsWe identified proteins that bind to all linker histone variants and proteins that are specific for only one class of variant. The factors identified include histone chaperones, transcriptional regulators, RNA binding proteins and ribosomal proteins. The nuclear pore complex protein Tpr, which was found to associate with only replication-dependent linker histones, specifically promoted their stability.ConclusionReplication-dependent and replication-independent linker histone variants can interact with both common and distinct sets of proteins. Some of these factors are likely to function as histone chaperones while others may suggest novel links between linker histones and RNA metabolism. The nuclear pore complex protein Tpr specifically interacts with histone H1.1 and H1.2 but not H1x and can regulate the stability of these replication-dependent linker histones.Electronic supplementary materialThe online version of this article (doi:10.1186/s12858-016-0074-9) contains supplementary material, which is available to authorized users.
Highlights
There are 11 variants of linker histone H1 in mammalian cells
To explore in more detail the distinction between replication-dependent (H1.1 and H1.2) and replicationindependent (H1x) H1 variants, we examined whether the specificity observed for replication-dependent H1.1 and H1.2 displayed by Tpr was a reflection of a specific in vivo connection between Tpr and replicationdependent linker histones
It is important to note that in MG132 treated cells all H1 variants were still localized within the nucleus, indicating that loss of Tpr did not cause replication-dependent H1 proteins to accumulate in the cytosol suggesting that Tpr is not required for the nuclear import of replication-dependent linker histones. These results suggest that the specific interaction between Tpr and replication-dependent histone H1 variants detected biochemically is a reflection of a specific in vivo interaction
Summary
There are 11 variants of linker histone H1 in mammalian cells Beyond their shared abilities to stabilize and condense chromatin, the H1 variants have been found to have non-redundant functions, the mechanisms of which are not fully understood. The histone chaperones and other factors that regulate linker histone dynamics in the cell are largely unknown It is not known whether replication-dependent and replication-independent linker histones interact with distinct or common sets of proteins. The expression levels and activities of the H1 variants were found to be highly regulated during cell differentiation and tumorigenesis [6] These observations suggest the hypothesis that each H1 variant has its individual function in the cells in addition to their roles as global chromatin modifiers
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