In Vivo Phosphorylation of Histone H1 Variants during the Cell Cycle

Talasz, Heribert; Helliger, Wilfried; Puschendorf, Bernd; Lindner, Herbert

doi:10.1021/bi951914e

Cited by 87 publications

(85 citation statements)

References 33 publications

(47 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…5). In growth-arrested cells at G 1 phase, linker histones are unphosphorylated, whereas in late S phase, the H1 variants exist as a combination of molecules containing one to three phosphate groups, according to the particular subtype (15). The fastest migrating components in capillary electrophoresis are the unphosphorylated H1 histones (29,36) (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…The presence of this large number of various H1 histone subtypes and their possible posttranslational modifications, such as phosphorylation (15), make it very probable that H1 histones play numerous structural and functional roles in chromatin. Until now, no specific role for the various variants has been established although Kaludov et al (16) showed that the mouse histone H1b binds preferentially to a regulatory sequence within a mouse H3.2 replication-dependent histone gene.…”

mentioning

confidence: 99%

See 1 more Smart Citation

In Vitro Binding of H1 Histone Subtypes to Nucleosomal Organized Mouse Mammary Tumor Virus Long Terminal Repeat Promotor

Talasz

Sapojnikova²,

Helliger

et al. 1998

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

The binding of all known linker histones, named H1a through H1e, including H1 0 and H1t, to a model chromatin complex based on a DNA fragment containing the mouse mammary tumor virus long terminal repeat promotor was systematically studied. As for the histone subtype H1b, we found a dissociation constant of 8 -16 nM to a single mononucleosome (210 base pairs), whereas the binding constant of all other subtypes varied between 2 and 4 nM. Most of the H1 histones, namely H1a, H1c, H1d/e, and H1 0 , completely aggregate polynucleosomes (1.3 kilobase pairs, 6 nucleosomes) at 270 -360 nM, corresponding to a molar ratio of six to eight H1 molecules per reconstituted nucleosome. To form aggregates with the histones H1t and H1b, however, greater amounts of protein were required. Furthermore, our results show that specific types of in vivo phosphorylation of the linker histone tails influence both the binding to mononucleosomes and the aggregation of polynucleosomes. S phase-specific phosphorylation with one to three phosphate groups at specific sites in the C terminus influences neither the binding to a mononucleosome nor the aggregation of polynucleosomes. In contrast, highly phosphorylated H1 histones with four to five phosphate groups in the C and N termini reveal a very high binding affinity to a mononucleosome but a low chromatin aggregation capability. These findings suggest that specific S phase or mitotic phosphorylation sites act independently and have distinct functional roles.H1 histones are a heterogeneous group of at least five subtypes with closely related but nonetheless different primary structures (1, 2). Two further H1 subtypes are known: the histone H1 0 , which is found in nonreplicative tissues (3, 4) and in rapidly proliferating cells (5), and the testis-specific histone variant H1t (6). The various linker histones containing a globular central region flanked by highly basic and hydrophilic C-and N-terminal tails (7,8) bind to the nucleosome and promote the organization of nucleosomes to a higher order structure (9, 10).There is evidence that histone H1 may interact differently with transcriptionally active and inactive regions of chromatin (11). Linker histones are also thought to modulate nucleosome position (12, 13) and to influence replication efficiency in vitro (14).The presence of this large number of various H1 histone subtypes and their possible posttranslational modifications, such as phosphorylation (15), make it very probable that H1 histones play numerous structural and functional roles in chromatin. Until now, no specific role for the various variants has been established although Kaludov et al. (16) showed that the mouse histone H1b binds preferentially to a regulatory sequence within a mouse H3.2 replication-dependent histone gene. Previous analysis of the structural role of H1 histones demonstrated that three subfractions of H1 histones differ in their effectiveness in condensing DNA fibers into ordered aggregates (17) and that histone subtype H1t, compared with other subtypes, dif...

show abstract

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

In Vitro Binding of H1 Histone Subtypes to Nucleosomal Organized Mouse Mammary Tumor Virus Long Terminal Repeat Promotor

Talasz

Sapojnikova²,

Helliger

et al. 1998

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

show abstract

“…For isolation of histones, nuclei from NIH fibroblasts were prepared as described. 13 H1 histones were isolated from the resulting nuclear preparations by extracting with 5% perchloric acid at 48C for 1 h. The mixture was centrifuged at 10 0006g for 20 min. The remaining pellet was resuspended with 0.4 M H 2 SO 4 at 48C for 1 h to extract the core histones.…”

Section: Labeling Conditions and Isolation Of H1 And Core Histonesmentioning

confidence: 99%

“…12 The cdc 2/H1 kinase-dependent phosphorylation of H1 histones during the cell cycle is a dynamic process with a phosphorylation maximum during mitosis. 13 Whereas H2A histones are constantly phosphorylated, phosphorylation of H4 and H2B histones is negligible throughout the cell cycle. Histone H3 phosphorylation, in particular, appears to be essential for proper mitotic chromosome condensation and segregation, 14,15 but was also shown to be involved in premature chromosome condensation.…”

Section: Introductionmentioning

confidence: 99%

Hyperphosphorylation of histone H2A.X and dephosphorylation of histone H1 subtypes in the course of apoptosis

et al. 2002

View full text Add to dashboard Cite

Chromatin condensation paralleled by DNA fragmentation is one of the most important nuclear events occurring during apoptosis. Histone modifications, and in particular phosphorylation, have been suggested to affect chromatin function and structure during both cell cycle and cell death. We report here that phosphate incorporation into all H1 subtypes decreased rapidly after induction of apoptosis, evidently causing a strong reduction in phosphorylated forms of main H1 histone subtypes. H1 dephosphorylation is accompanied by chromatin condensation preceding the onset of typical chromatin oligonucleosomal fragmentation, whereas H2A.X hyperphosphorylation is strongly correlated to apoptotic chromatin fragmentation. Using various kinase inhibitors we were able to exclude some of the possible kinases which can be involved directly or indirectly in phosphorylation of histone H2A.X. Neither DNA-dependent protein kinase, protein kinase A, protein kinase G, nor the kinases driven by the mitogenactivated protein kinase (MAP) pathway appear to be responsible for H2A.X phosphorylation. The protein kinase C activator phorbol 12-myristate 13-acetate (PMA), however, markedly reduced the induction of apoptosis in TNFa-treated cells with a simultaneous change in the phosphorylation pattern of histone H2A.X. Hyperphosphorylation of H2A.X in apoptotic cells depends indirectly on activation of caspases and nuclear scaffold proteases as shown in zVAD-(OMe)-fmkor zAPF-cmk-treated cells, whereas the dephosphorylation of H1 subtypes seems to be influenced solely by caspase inhibitors. Together, these results illustrate that H1 dephosphorylation and H2A.X hyperphosphorylation are necessary steps on the apoptotic pathway.

show abstract

“…H1 histones are phosphorylated at multiple sites in the N-and C-terminal tails, in a cell cycle dependent manner. During G1 phase, H1 phosphorylation is low, while addition of phosphate groups increases during the S-and G2-phases to reach maximum at the M-phase (17). This is executed by one or more kinases, for example, CDK2 (18).…”

mentioning

confidence: 99%

Translocation of histone H1 subtypes between chromatin and cytoplasm during mitosis in normal human fibroblasts

et al. 2010

View full text Add to dashboard Cite

Histone H1 is an important constituent of chromatin, which undergoes major structural rearrangements during mitosis. However, the role of H1, multiple H1 subtypes, and H1 phosphorylation is still unclear. In normal human fibroblasts, phosphorylated H1 was found located in nuclei during prophase and in both cytoplasm and condensed chromosomes during metaphase, anaphase, and telophase as detected by immunocytochemistry. Moreover, we detected remarkable differences in the distribution of the histone H1 subtypes H1.2, H1.3, and H1.5 during mitosis. H1.2 was found in chromatin during prophase and almost solely in the cytoplasm of metaphase and early anaphase cells. In late anaphase, it appeared in both chromatin and cytoplasm and again in chromatin during telophase. H1.5 distribution pattern resembled that of H1.2, but H1.5 was partitioned between chromatin and cytoplasm during metaphase and early anaphase. H1.3 was detected in chromatin in all cell cycle phases. We propose therefore, that H1 subtype translocation during mitosis is controlled by phosphorylation, in combination with H1 subtype inherent affinity. We conclude that H1 subtypes, or their phosphorylated forms, may leave chromatin in a regulated way to give access for chromatin condensing factors or transcriptional regulators during mitosis. ' 2010International Society for Advancement of Cytometry Key terms histone H1; chromatin; cell cycle; mitosis IN the cell cycle, DNA and protein content are duplicated, and the cell divides in two in a strict sequential order of events. During prophase, the replicated chromosomes condense, and the nuclear membrane breaks down in prometaphase. At metaphase, the chromosomes are aligned at the equator of the mitotic spindle, and the sister chromatids are segregated to the two poles of the spindle during anaphase. Finally, the separation is completed during telophase by cytoplasmic division. Impaired cell cycle control or cell cycle progression may result in cell death or malignant transformation.

show abstract

In Vivo Phosphorylation of Histone H1 Variants during the Cell Cycle

Cited by 87 publications

References 33 publications

In Vitro Binding of H1 Histone Subtypes to Nucleosomal Organized Mouse Mammary Tumor Virus Long Terminal Repeat Promotor

In Vitro Binding of H1 Histone Subtypes to Nucleosomal Organized Mouse Mammary Tumor Virus Long Terminal Repeat Promotor

Hyperphosphorylation of histone H2A.X and dephosphorylation of histone H1 subtypes in the course of apoptosis

Translocation of histone H1 subtypes between chromatin and cytoplasm during mitosis in normal human fibroblasts

Contact Info

Product

Resources

About