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Rundquist, Ingemar
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Publications (10 of 18) Show all publications
Kostova-Koleva, N. N., Srebreva, L., Markov, D. V., Sarg, B., Lindner, H. H. & Rundquist, I. (2013). Histone H5chromatin interactions in situ are strongly modulated by H5 C-terminal phosphorylation. Cytometry Part A, 83A(3), 273-279
Open this publication in new window or tab >>Histone H5chromatin interactions in situ are strongly modulated by H5 C-terminal phosphorylation
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2013 (English)In: Cytometry Part A, ISSN 1552-4922, E-ISSN 1552-4930, Vol. 83A, no 3, p. 273-279Article in journal (Refereed) Published
Abstract [en]

We used linker histone-depleted normal human fibroblast nuclei as templates to study how phosphorylation affects histone H5 binding to chromatin in situ. Permeabilized cells were treated with 0.7 M NaCl to extract the native linker histones. Histone H5 was purified from chicken erythrocytes and phosphorylated in vitro by recombinant cdk5/p35 kinase. High performance capillary electrophoresis (HPCE) showed that the phosphorylated protein contained a mixture of multiply phosphorylated forms. Control experiments, using mass spectrometry, revealed that up to five SPXK motifs in the C terminus were phosphorylated, but also that about 10% of the protein contained one phosphoserine in the N-terminus. Reconstitution of H1-depleted fibroblast nuclei with nonphosphorylated or phosphorylated H5 was performed at physiological ionic strength. The bound H5 was then extracted using NaCl concentrations in the range of 0.15 to 0.7 M. The release of the H5 molecules was monitored by DAPI staining and image cytofluorometry. Our results show that H5 phosphorylation substantially reduced its affinity for chromatin in situ, which support previous observations indicating that C-terminal phosphorylation may be essential for the biological functions of linker histones.

Place, publisher, year, edition, pages
Wiley-Blackwell, 2013
Keywords
chromatin, linker histones, affinity, phosphorylation
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-90191 (URN)10.1002/cyto.a.22221 (DOI)000315299000004 ()
Note

Funding Agencies|Bulgarian National Science Fund|K-906/1999|Swedish Research Council|349-2001-6688|European Science Foundation EUROCORES Programme EuroDYNA (Austrian Science Foundation)|I23-B03|EC Sixth Framework Programme|ERAS-CT-2003-980409|

Available from: 2013-03-26 Created: 2013-03-21 Last updated: 2017-12-06
Gréen, A., Sarg, B., Green, H., Lönn, A., Lindner, H. H. & Rundquist, I. (2011). Histone H1 interphase phosphorylation becomes largely established in G(1) or early S phase and differs in G(1) between T-lymphoblastoid cells and normal T cells. EPIGENETICS and CHROMATIN, 4(15)
Open this publication in new window or tab >>Histone H1 interphase phosphorylation becomes largely established in G(1) or early S phase and differs in G(1) between T-lymphoblastoid cells and normal T cells
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2011 (English)In: EPIGENETICS and CHROMATIN, ISSN 1756-8935, Vol. 4, no 15Article in journal (Refereed) Published
Abstract [en]

Background: Histone H1 is an important constituent of chromatin, and is involved in regulation of its structure. During the cell cycle, chromatin becomes locally decondensed in S phase, highly condensed during metaphase, and again decondensed before re-entry into G(1). This has been connected to increasing phosphorylation of H1 histones through the cell cycle. However, many of these experiments have been performed using cell-synchronization techniques and cell cycle-arresting drugs. In this study, we investigated the H1 subtype composition and phosphorylation pattern in the cell cycle of normal human activated T cells and Jurkat T-lymphoblastoid cells by capillary electrophoresis after sorting of exponentially growing cells into G(1), S and G(2)/M populations. less thanbrgreater than less thanbrgreater thanResults: We found that the relative amount of H1.5 protein increased significantly after T-cell activation. Serine phosphorylation of H1 subtypes occurred to a large extent in late G(1) or early S phase in both activated T cells and Jurkat cells. Furthermore, our data confirm that the H1 molecules newly synthesized during S phase achieve a similar phosphorylation pattern to the previous ones. Jurkat cells had more extended H1.5 phosphorylation in G(1) compared with T cells, a difference that can be explained by faster cell growth and/or the presence of enhanced H1 kinase activity in G(1) in Jurkat cells. less thanbrgreater than less thanbrgreater thanConclusion: Our data are consistent with a model in which a major part of interphase H1 phosphorylation takes place in G(1) or early S phase. This implies that H1 serine phosphorylation may be coupled to changes in chromatin structure necessary for DNA replication. In addition, the increased H1 phosphorylation of malignant cells in G(1) may be affecting the G(1)/S transition control and enabling facilitated S-phase entry as a result of relaxed chromatin condensation. Furthermore, increased H1.5 expression may be coupled to the proliferative capacity of growth-stimulated T cells.

Place, publisher, year, edition, pages
BioMed Central, 2011
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-71559 (URN)10.1186/1756-8935-4-15 (DOI)000295461100001 ()
Note
Funding Agencies|Austrian Science Foundation| I23-B03 |EC Sixth Framework Programme| ERAS-CT-2003-980409 |Swedish Cancer Society||Available from: 2011-10-21 Created: 2011-10-21 Last updated: 2011-10-24
Gréen,, A., Lönn, A., Holmgren Peterson, K., Öllinger, K. & Rundquist, I. (2010). Translocation of Histone H1 Subtypes Between Chromatin and Cytoplasm During Mitosis in Normal Human Fibroblasts. Cytometry Part A, 77A(5), 478-484
Open this publication in new window or tab >>Translocation of Histone H1 Subtypes Between Chromatin and Cytoplasm During Mitosis in Normal Human Fibroblasts
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2010 (English)In: Cytometry Part A, ISSN 1552-4922, E-ISSN 1552-4930, Vol. 77A, no 5, p. 478-484Article in journal (Refereed) Published
Abstract [en]

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 some H1.5 remained situated in chromatin 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 variants, may be signalling molecules in mitosis or that they leave chromatin in a regulated way to give access for chromatin condensing factors or transcriptional regulators during mitosis.

Place, publisher, year, edition, pages
John Wiley & Sons, 2010
Keywords
Histone H1, Chromatin, Cell cycle, Mitosis
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-16383 (URN)10.1002/cyto.a.20851 (DOI)000277174000009 ()20104577 (PubMedID)
Available from: 2009-01-20 Created: 2009-01-20 Last updated: 2017-12-14Bibliographically approved
Gréen, A., Sarg, B., Koutzamani, E., Genheden, U., Lindner, H. H. . & Rundquist, I. (2008). Histone H1 Dephosphorylation Is Not a General Feature in Early Apoptosis. Biochemistry, 47, 7539-7547
Open this publication in new window or tab >>Histone H1 Dephosphorylation Is Not a General Feature in Early Apoptosis
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2008 (English)In: Biochemistry, ISSN 0006-2960, E-ISSN 1520-4995, Vol. 47, p. 7539-7547Article in journal (Refereed) Published
Abstract [en]

Histone H1 is a family of nucleosomal proteins that exist in a number of subtypes. These subtypes can be modified after translation in various ways, above all by phosphorylation. Increasing levels of H1 phosphorylation has been correlated with cell cycle progression, while both phosphorylation and dephosphorylation of histone H1 have been linked to the apoptotic process. Such conflicting results may depend on which various apoptosis-inducing agents cause apoptosis via different apoptotic pathways and often interfere with cell proliferation. Therefore, we investigated the relation between apoptosis and H1 phosphorylation in Jurkat cells after apoptosis induction via both the extrinsic and intrinsic pathways and by taking cell cycle effects into account. After apoptosis induction by anti-Fas, no significant dephosphorylation, as measured by capillary electrophoresis, or cell cycle-specific effects were detected. In contrast, H1 subtypes were rapidly dephosphorylated when apoptosis was induced by camptothecin. We conclude that histone H1 dephosphorylation is not connected to apoptosis in general but may be coupled to apoptosis by the intrinsic pathway or to concomitant growth inhibitory signaling.

Place, publisher, year, edition, pages
ACS Publications, 2008
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-16382 (URN)10.1021/bi702311x (DOI)
Available from: 2009-01-20 Created: 2009-01-20 Last updated: 2017-12-14Bibliographically approved
Rundquist, I. & Lindner, H. H. (2006). Analyses of linker histone - chromatin interactions in situ. Biochemistry and Cell Biology, 84(4), 427-436
Open this publication in new window or tab >>Analyses of linker histone - chromatin interactions in situ
2006 (English)In: Biochemistry and Cell Biology, ISSN 0829-8211, E-ISSN 1208-6002, Vol. 84, no 4, p. 427-436Article in journal (Refereed) Published
Abstract [en]

Recent studies, using cytometric techniques based on fluorescence microscopy, have provided new information on how linker histones interact with chromatin in vivo or in situ. In particular, the use of green fluorescent proteins (GFPs) has enabled detailed studies of how individual H1 subtypes, and specific motifs in them, interact with chromatin in vivo. Furthermore, the development of cytochemical methods to study the interaction between linker histones and chromatin using DNA-binding fluorochromes as indirect probes for linker histone affinity in situ, in combination with highly sensitive and specific analytical methods, has provided additional information on the interactions between linker histones and chromatin in several cell systems. Such results verified that linker histones have a substantially higher affinity for chromatin in mature chicken erythrocytes than in frog erythrocytes, and they also indicated that the affinity decreased during differentiation of the frog erythrocytes. Furthermore, in cultured human fibroblasts, the linker histones showed a relatively high affinity for chromatin in interphase, whereas it showed a significantly lower affinity in highly condensed metaphase chromosomes. This method also enables the analysis of linker histone affinity for chromatin in H1-depleted fibroblasts reconstituted with purified linker histones. No consistent correlation between linker histone affinity and chromatin condensation has so far been detected.

Keywords
chromatin, linker histones, image cytofluorometry, high-performance capillary electrophoresis, hydrophillic interaction, liquid chromatography
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-45998 (URN)10.1139/O06-071 (DOI)
Available from: 2009-10-11 Created: 2009-10-11 Last updated: 2017-12-13
Sarg, B., Gréen, A. ., Söderkvist, P., Helliger, W. ., Rundquist, I. . & Lindner, H. H. . (2005). Characterization of sequence variations in human histone H1.2 and H1.4 subtypes. The FEBS Journal, 272(14), 3673 -3683
Open this publication in new window or tab >>Characterization of sequence variations in human histone H1.2 and H1.4 subtypes
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2005 (English)In: The FEBS Journal, ISSN 1742-464X, E-ISSN 1742-4658, Vol. 272, no 14, p. 3673 -3683Article in journal (Refereed) Published
Abstract [en]

In humans, eight types of histone H1 exist (H1.1–H1.5, H1°, H1t and H1oo), all consisting of a highly conserved globular domain and less conserved N- and C-terminal tails. Although the precise functions of these isoforms are not yet understood, and H1 subtypes have been found to be dispensable for mammalian development, it is now clear that specific functions may be assigned to certain individual H1 subtypes. Moreover, microsequence variations within the isoforms, such as polymorphisms or mutations, may have biological significance because of the high degree of sequence conservation of these proteins. This study used a hydrophilic interaction liquid chromatographic method to detect sequence variants within the subtypes. Two deviations from wild-type H1 sequences were found. In K562 erythroleukemic cells, alanine at position 17 in H1.2 was replaced by valine, and, in Raji B lymphoblastoid cells, lysine at position 173 in H1.4 was replaced by arginine. We confirmed these findings by DNA sequencing of the corresponding gene segments. In K562 cells, a homozygous GCC→GTC shift was found at codon 18, giving rise to H1.2 Ala17Val because the initial methionine is removed in H1 histones. Raji cells showed a heterozygous AAA→AGA codon change at position 174 in H1.4, corresponding to the Lys173Arg substitution. The allele frequency of these sequence variants in a normal Swedish population was found to be 6.8% for the H1.2 GCC→GTC shift, indicating that this is a relatively frequent polymorphism. The AAA→AGA codon change in H1.4 was detected only in Raji cells and was not present in a normal population or in six other cell lines derived from individuals suffering from Burkitt's lymphoma. The significance of these sequence variants is unclear, but increasing evidence indicates that minor sequence variations in linker histones may change their binding characteristics, influence chromatin remodeling, and specifically affect important cellular functions.

Place, publisher, year, edition, pages
Wiley InterScience, 2005
Keywords
HILIC, linker histones, sequence variants, SNP, tumor cell lines
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-16381 (URN)10.1111/j.1742-4658.2005.04793.x (DOI)
Available from: 2009-01-20 Created: 2009-01-20 Last updated: 2017-12-14Bibliographically approved
Kostova, N., Srebreva, L. N., Milev, A. D., Bogdanova, O. G., Rundquist, I., Lindner, H. H. & Markov, D. V. (2005). Immunohistochemical demonstration of histone H10 in human breast carcinoma. Histochemistry and Cell Biology, 124(5), 435-443
Open this publication in new window or tab >>Immunohistochemical demonstration of histone H10 in human breast carcinoma
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2005 (English)In: Histochemistry and Cell Biology, ISSN 0948-6143, E-ISSN 1432-119X, Vol. 124, no 5, p. 435-443Article in journal (Refereed) Published
Abstract [en]

Histone H10 is a linker histone subvariant present in tissues of low proliferation rate. It is supposed to participate in the expression and maintenance of the terminal differentiation phenotype. The aim of this work was to study histone H10 distribution in human breast carcinoma and its relationship with the processes of proliferation and differentiation. Most of the cells in carcinomas of moderate and high level of differentiation expressed histone H10 including cells invading connective and adipose tissues. In low differentiated tumours, the number of H10 expressing cells was considerably lower. Staining of myoepithelial cells, when seen, and of stromal fibroblasts was variable. The metastatic malignant cells in the lymph nodes also accumulated H10 but lymphocytes were always negative. All immunopositive malignant cells exhibited signs of polymorphism. Double H1 0/Ki-67 staining showed that the growth fraction in more differentiated tumours belonged to the H10-positive cells, while in poorly differentiated carcinomas it also included a cell subpopulation not expressing H10. If expressed, p27Kip1 was always found in H10-positive cells. These findings are inconsistent with the widespread view that histone H10 is expressed only in terminally differentiated cells. Rather, they suggest that the protein is expressed in cells in a prolonged intermitotic period irrespective of their level of differentiation. Double H10/Ki-67 immunostaining could be a useful tool in studying the growth fraction in tumours. © Springer-Verlag 2005.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-30888 (URN)10.1007/s00418-005-0052-6 (DOI)16550 (Local ID)16550 (Archive number)16550 (OAI)
Available from: 2009-10-09 Created: 2009-10-09 Last updated: 2017-12-13
Kostova, N., Srebreva, L., Markov, D. & Rundquist, I. (2004). Histone H1 and chromatin interactions in human fibroblast nuclei after H1 depletion and reconstitution with H1 subfractions. Cytometry, 58A(2), 132-139
Open this publication in new window or tab >>Histone H1 and chromatin interactions in human fibroblast nuclei after H1 depletion and reconstitution with H1 subfractions
2004 (English)In: Cytometry, ISSN 0196-4763, E-ISSN 1097-0320, Vol. 58A, no 2, p. 132-139Article in journal (Refereed) Published
Abstract [en]

Background: Linker histones constitute a family of lysine-rich proteins associated with nucleosome core particles and linker DNA in eukaryotic chromatin. In permeabilized cells, they can be extracted from nuclei by using salt concentration in the range of 0.3 to 0.7 M. Although other nuclear proteins are also extracted at 0.7 M salt, the remaining nucleus represents a template that is relatively intact. Methods: A cytochemical method was used to study the affinity of reconstituted linker histones for chromatin in situ in cultured human fibroblasts. We also investigated their ability to condense chromatin by using DNA-specific osmium ammine staining for electron microscopy. Results: Permeabilized and H1-depleted fibroblast nuclei were suitable for the study of linker histone-chromatin interactions after reconstitution with purified linker histone subfractions. Our results showed that exogenous linker histones bind to chromatin with lower affinity than the native ones. We detected no significant differences between the main H1 and H1degrees histone fractions with respect to their affinity for chromatin or in their ability to condense chromatin. Conclusions: Linker histone interactions with chromatin are controlled also by mechanisms independent of linker histone subtype composition. (C) 2004 Wiley-Liss, Inc.

Keywords
chromatin, linker histones, binding, affinity, 4 ', 6-diamidino-2-phenylindole, image cytofluorometry
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-46247 (URN)10.1002/cyto.a.10119 (DOI)
Available from: 2009-10-11 Created: 2009-10-11 Last updated: 2017-12-13
Brynhildsen, J., Dahle, C., Behrbohm Fallsberg, M., Rundquist, I. & Hammar, M. (2002). Attitudes among students and teachers on vertical integration between clinical medicine and basic science within a problem-based undergraduate medical curriculum. Medical teacher, 24(3), 286-288
Open this publication in new window or tab >>Attitudes among students and teachers on vertical integration between clinical medicine and basic science within a problem-based undergraduate medical curriculum
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2002 (English)In: Medical teacher, ISSN 0142-159X, E-ISSN 1466-187X, Vol. 24, no 3, p. 286-288Article in journal (Refereed) Published
Abstract [en]

Important elements in the curriculum at the Faculty of Health Sciences in Link÷ping are vertical integration, i.e. integration between the clinical and basic science sections of the curriculum, and horizontal integration between different subject areas. Integration throughout the whole curriculum is time-consuming for both teachers and students and hard work is required for planning, organization and execution. The aim was to assess the importance of vertical and horizontal integration in an undergraduate medical curriculum, according to opinions among students and teachers. In a questionnaire 102 faculty teachers and 106 students were asked about the importance of 14 different components of the undergraduate medical curriculum including vertical and horizontal integration. They were asked to assign between one and six points to each component (6 points = extremely important for the quality of the curriculum, 1 point = unimportant). Students as well as teachers appreciated highly both forms of integration. Students scored horizontal integration slightly but significantly higher than the teachers (median 6 vs 5 points, p=0.009, Mann-Whitney U-test), whereas teachers scored vertical integration higher than students (6 vs 5, p=0.019, Mann-Whitney U-test). Both students and teachers considered horizontal and vertical integration to be highly important components of the undergraduate medical programme. We believe both kinds of integration support problem-based learning and stimulate deep and lifelong learning and suggest that integration should always be considered deeply when a new curriculum is planned for undergraduate medical education.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-25337 (URN)10.1080/01421590220134105 (DOI)9779 (Local ID)9779 (Archive number)9779 (OAI)
Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2017-12-13
Koutzamani, E., Borg, H., Sarg, B., Lindner, H. & Rundquist, I. (2002). Linker histone subtype composition and affinity for chromatin in situ in nucleated mature erythrocytes. Journal of Biological Chemistry, 277(47), 44688-44694
Open this publication in new window or tab >>Linker histone subtype composition and affinity for chromatin in situ in nucleated mature erythrocytes
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2002 (English)In: Journal of Biological Chemistry, ISSN 0021-9258, Vol. 277, no 47, p. 44688-44694Article in journal (Refereed) Published
Abstract [en]

The replacement linker histones H10 and H5 are present in frog and chicken erythrocytes, respectively, and their accumulation coincides with cessation of proliferation and compaction of chromatin. These cells have been analyzed for the affinity of linker histones for chromatin with cytochemical and biochemical methods. Our results show a stronger association between linker histones and chromatin in chicken erythrocyte nuclei than in frog erythrocyte nuclei. Analyses of linker histones from chicken erythrocytes using capillary electrophoresis showed H5 to be the subtype strongest associated with chromatin. The corresponding analyses of frog erythrocyte linker histones using reverse-phase high performance liquid chromatography showed that H10 dissociated from chromatin at somewhat higher ionic strength than the three additional subtypes present in frog blood but at lower ionic strength than chicken H5. Which of the two H10 variants in frog is expressed in erythrocytes has thus far been unknown. Amino acid sequencing showed that H10-2 is the only H10 subtype present in frog erythrocytes and that it is 100% acetylated at its N termini. In conclusion, our results show differences between frog and chicken linker histone affinity for chromatin probably caused by the specific subtype composition present in each cell type. Our data also indicate a lack of correlation between linker histone affinity and chromatin condensation.

 

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-14128 (URN)10.1074/jbc.M203533200 (DOI)
Available from: 2006-11-06 Created: 2006-11-06 Last updated: 2009-05-25
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