H1 subtype expression during cell proliferation and growth arrest

Abstract

H1 histone subtype genes differ in their expression patterns during the different stages of the cell cycle interphase. While the group of replication-dependent H1 histone subtypes is synthesized during S phase, the replacement histone subtype H1.0 is also expressed replication-independently in non-proliferating cells. The present study is the first report about the analysis of the cell cycle-dependent expression of all five replication-dependent H1 subtypes, the replacement histone H1.0 and the ubiquitously expressed subtype H1x. The expression of these H1 histone subtypes in HeLa cells was analyzed on mRNA level by quantitative real-time RT-PCR as well as on protein level by immunoblotting. We found that after arrest of HeLa cells in G(1) phase by treatment with sodium butyrate, the mRNA levels of all replication-dependently expressed H1 subtypes decreased, but to very different extent. During S phase the individual replication-dependently expressed H1 subtypes show similar kinetics regarding their mRNA levels. However, the variations in their protein amounts partially differ from the respective RNA levels which especially applies to histone H1.3. In contrast, the mRNA as well as the protein level of H1x remained nearly unchanged in G(1) as well as during S phase progression. The results of the present study demonstrate that the cell cycle-dependent mRNA and protein expression of various H1 subtypes is differentially regulated, supporting the hypothesis of a functional heterogeneity.

Linker Histone H1.2 Cooperates with Cul4A and PAF1 to Drive H4K31 Ubiquitylation-Mediated Transactivation

“…These results indicate that the presence of WDR5 in H1-associated complexes does not solely depend on its ability to interact with the Cul4A. Because H1.1 is minimally expressed in HeLa cells (Happel et al, 2009 and Figure S1A), the physiological significance of H1.1 data obtained in our purification could be questioned. For this reason, we decided to focus on the H1.2 interactions with the Cul4A and PAF1 complexes in the present study.…”

Linker histone subtypes and their allelic variants

“…The readily mobilized histone H1.2 and restricted mobilization of histone H1.0 seem to be biologically relevant for lytic HSV‐1 and latent infections respectively (Conn et al, 2008). The functional heterogeneity of histone H1 subtypes was supported by Happel et al (2009) who showed different expression patterns of individual histone H1 subtypes during cell cycle progression in HeLa cells. Although mRNA levels of somatic replication‐dependent subtypes (H1.1–H1.5) decreased after butyrate‐induced arrest of the cell cycle, both the H1.5 mRNA and protein levels significantly declined compared with the remaining somatic subtypes, in agreement with the observation (Lennox and Cohen, 1983) that the histones H1.1 and H1.5 decrease in quiescent cells.…”

“…Although mRNA levels of somatic replication‐dependent subtypes (H1.1–H1.5) decreased after butyrate‐induced arrest of the cell cycle, both the H1.5 mRNA and protein levels significantly declined compared with the remaining somatic subtypes, in agreement with the observation (Lennox and Cohen, 1983) that the histones H1.1 and H1.5 decrease in quiescent cells. The butyrate‐induced arrest of the HeLa cell cycle in G 0 /G 1 phase led to a biphasic response of the replacement histone H1.0 since at first an increase in mRNA level and then a gradual increase in protein level were observed (Happel et al, 2009). Unlike the histone H1.0 and replication‐dependent histone H1 subtypes, the mRNA and protein levels of ubiquitously expressed histone H1x were nearly unaltered upon arresting the cell cycle.…”

“…Unlike the histone H1.0 and replication‐dependent histone H1 subtypes, the mRNA and protein levels of ubiquitously expressed histone H1x were nearly unaltered upon arresting the cell cycle. During S phase progression (Happel et al, 2009) the mRNA and protein amount of histone subtypes H1.2, H1.4 and H15 increased until mid‐S phase, and then the mRNA levels declined while the protein levels remained stable. At the end of the S phase an enhanced synthesis of H1.0 and H1.3 protein occurred, followed by a decline in their mRNAs.…”

Modulation of chromatin function through linker histone H1 variants

“…Experimental data point out that histone H1 exerts a subtype‐specific impact both on the DNA binding (Orrego et al., ) and chromatin condensation (Clausell et al., ). Moreover, the individual histone H1 subtypes affect many important cellular processes, including apoptosis (Konishi et al., ; Garg et al., ), differentiation (Terme et al., ), cell cycle progression and proliferation (Stoldt et al., ; Happel et al., ). Such differential histone H1 effects likely result from the combined impact of numerous factors which set the specific patterns for histone H1 subtype functioning.…”