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Gene Review

HIST1H1B  -  histone cluster 1, H1b

Homo sapiens

Synonyms: H1, H1.5, H1B, H1F5, H1b, ...
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Disease relevance of HIST1H1B


Psychiatry related information on HIST1H1B


High impact information on HIST1H1B


Chemical compound and disease context of HIST1H1B

  • The effect of doxorubicin (DX) treatment on H1 synthesis and acetylation was studied in two human colon adenocarcinoma cell lines, sensitive (LoVo) and resistant (LoVo/DX) to this drug [10].
  • The second pattern was observed in 18/19 chlorpromazine-treated patients and 14/17 patients with hydralazine-induced lupus in which IgM antibodies displayed more reactivity with DNA-free histones than with the corresponding histone-DNA complexes and almost no binding to H1-stripped chromatin [11].
  • A protein showing lower electrophoretic mobility in acidic urea polyacrylamide gels than did the usual histone H1 subfractions has been detected among the H1 histones extracted from chromatin of a transplantable hamster hepatoma, originally induced by Kirkman and Robbins [12].
  • In contrast to the vaccinia H1 phosphatase, CL100 shows no measurable catalytic activity towards a number of other substrate proteins modified on serine, threonine or tyrosine residues [13].
  • CL100 is a member of an expanding family of protein tyrosine phosphatases with amino acid sequence similarity to a Tyr/Ser-protein phosphatase encoded by the late H1 gene of vaccinia virus [13].

Biological context of HIST1H1B

  • The phosphorylation sites of histone H1.5 from mitotically enriched cells were also examined [14].
  • Our data suggest that phosphorylation of human H1 variants occurs nonrandomly during both interphase and mitosis and that distinct serine- or threonine-specific kinases are involved in different cell cycle phases [14].
  • All known human H1 histone genes except the H1(0) gene are clustered on chromosome 6 [15].
  • Deletion of the N terminus of the KSHV-cyclin affects the substrate specificity indicating that the N terminus is required for phosphorylation of histone H1 but not for other substrates [16].
  • To complete the set of the human H1 histone genes, we have designed two PCR primers deduced from a partially published sequence of the remaining histone H1 gene [Carozzi et al. (1984) Science 224, 1115-1118] and from a consensus sequence which we have derived from the conserved region of human histone H1 genes [17].

Anatomical context of HIST1H1B

  • H1 histones, isolated from logarithmically growing and mitotically enriched human lymphoblastic T-cells (CCRF-CEM), were fractionated by reversed phase and hydrophilic interaction liquid chromatography, subjected to enzymatic digestion, and analyzed by amino acid sequencing and mass spectrometry [14].
  • Varied expression patterns of human H1 histone genes in different cell lines [18].
  • Five main type H1 histones have been described in man (H1.1-H1.5) in addition to the testis specific type H1t and the replacement subtype H1 degrees, which is found mainly in highly differentiated cells [18].
  • Histone H1 isoforms isolated from asynchronously grown HeLa cells were subjected to enzymatic digestion and analyzed by nano-flow reversed-phase high performance liquid chromatography (RP-HPLC) tandem mass spectrometry (MS/MS) on both quadrupole ion trap and linear quadrupole ion trap-Fourier transform ion cyclotron resonance mass spectrometers [19].
  • The human H1 histone gene FNC16 is functionally expressed in proliferating HeLa S3 cells and is down-regulated during terminal differentiation in HL60 cells [20].

Associations of HIST1H1B with chemical compounds

  • 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 [21].
  • Specific inhibition of p40MO15 synthesis in stage VI oocytes by antisense oligonucleotide depletion of MO15 mRNA increases the rate of progesterone induced H1 kinase activation and oocyte maturation [22].
  • No lag phase was detected between the time when cyclin A was added and the time when H1 histone kinase activity was produced in frog extracts, even in the presence of 2 mM vanadate, which blocks cdc25 activity [23].
  • To analyze the effect of H1 tail phosphorylation on the modulation of the histone's nuclear dynamics, we generated a mutant histone H1, referred to as M1-5, in which the five cyclin-dependent kinase phosphorylation consensus sites were mutated from serine or threonine residues into alanines [24].
  • Glycerol gradient analyses demonstrated that the purified cdk2 (p33) protein co-sedimented with a cyclin A-dependent H1 kinase activity [25].

Physical interactions of HIST1H1B

  • It has been suggested that Cdk2 bound with cyclin D1 and Cdk2-cyclin-D1 complex show neither H1 histone nor pRB kinase activity [26].
  • Cyclin D2-CDK2 complexes increased in amounts but were inactive as histone H1 kinases in quiescent cells [27].
  • E1 also bound in vitro to H1 isolated under native conditions in association with intact nucleosomes [5].

Enzymatic interactions of HIST1H1B

  • These data suggest that CDK2 phosphorylates histone H1 in vivo, resulting in a more open chromatin structure by destabilizing H1-chromatin interactions [24].
  • Thus, cdk2 and cyclin A proteins are components that assemble to yield a kinase complex that catalyzes the phosphorylation of histone H1 [25].
  • Coincident with this decrease in newly synthesized cdc2 protein was a marked reduction in its ability to phosphorylate histone H1 [28].
  • The cyclin encoded by Kaposi's sarcoma-associated herpesvirus stimulates cdk6 to phosphorylate the retinoblastoma protein and histone H1 [29].
  • Cyclin/kinase complexes containing cyclins A or E are active primarily in late G1 to S phase and both have been shown to phosphorylate histone H1 and the retinoblastoma gene product (pRb) in vitro [30].

Regulatory relationships of HIST1H1B


Other interactions of HIST1H1B

  • All of the histone H1 genes are in HIST1, which is spread over about 2 Mb [32].
  • With the exception of H1.2 and H1.4, we found substantial differences between the H1 mRNA levels in the different cell lines tested [18].
  • We have previously located the genes of the five human main type H1 genes and the gene encoding the testicular subtype H1t to the region 21.1 to 22.2 on the short arm of chromosome 6 [33].
  • The analysis showed a differential rise of mRNA levels during S-phase, from four-fold (H1 degrees) to 15-fold (H1.5) [18].
  • PCNA immunoprecipitates possessed H1 histone kinase activity, which increased in parallel with increasing cellular content of PCNA [34].

Analytical, diagnostic and therapeutic context of HIST1H1B

  • To investigate the organization of the histone genes in this region, we isolated two YACs from a human YAC library by PCR screening with primers specific for histone H1 [33].
  • The immunoprecipitates of CG-NAP/D exhibited histone H1 kinase activity, suggesting the co-immunoprecipitation of active cyclin-cdk complexes [35].
  • Electrophoretic mobility-shift assay and DNase I footprinting analysis suggest that the H1-box variant AAACAGA is a potential control element within the distal promoter region [36].
  • Using a quantitative assay and electron microscopy with synthetic peptides, we show that, whereas the wild-type H1 peptide rapidly disassembles preformed keratin filaments in vitro, the mutant peptide does this far less efficiently [9].
  • We have studied the three-dimensional folding of the scaffolding in histone H1-depleted chromosomes by immunofluorescence with an antibody specific for topoisomerase II [37].


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  2. Modulation of cell cycle control by vitamin D3 and its analogue, EB1089, in human breast cancer cells. Wu, G., Fan, R.S., Li, W., Ko, T.C., Brattain, M.G. Oncogene (1997) [Pubmed]
  3. Progression of LNCaP prostate tumor cells during androgen deprivation: hormone-independent growth, repression of proliferation by androgen, and role for p27Kip1 in androgen-induced cell cycle arrest. Kokontis, J.M., Hay, N., Liao, S. Mol. Endocrinol. (1998) [Pubmed]
  4. Kaposi's sarcoma-associated herpesvirus encodes a functional cyclin. Li, M., Lee, H., Yoon, D.W., Albrecht, J.C., Fleckenstein, B., Neipel, F., Jung, J.U. J. Virol. (1997) [Pubmed]
  5. Association of the human papillomavirus type 11 E1 protein with histone H1. Swindle, C.S., Engler, J.A. J. Virol. (1998) [Pubmed]
  6. Alterations in human linker histone-DNA binding in the presence of aluminum salts in vitro and in Alzheimer's disease. Lukiw, W.J., Kruck, T.P., McLachlan, D.R. Neurotoxicology (1987) [Pubmed]
  7. Gene regulation by histone H1: new links to DNA methylation. Rupp, R.A., Becker, P.B. Cell (2005) [Pubmed]
  8. Histone H1 depletion in mammals alters global chromatin structure but causes specific changes in gene regulation. Fan, Y., Nikitina, T., Zhao, J., Fleury, T.J., Bhattacharyya, R., Bouhassira, E.E., Stein, A., Woodcock, C.L., Skoultchi, A.I. Cell (2005) [Pubmed]
  9. A leucine----proline mutation in the H1 subdomain of keratin 1 causes epidermolytic hyperkeratosis. Chipev, C.C., Korge, B.P., Markova, N., Bale, S.J., DiGiovanna, J.J., Compton, J.G., Steinert, P.M. Cell (1992) [Pubmed]
  10. Doxorubicin induces the acetylation of histone H1 in a human colon cancer cell line (LoVo/DX) selected for resistance to the drug, but not in the sensitive parental line (LoVo). Mannironi, C., D'Incalci, M. Biochem. Biophys. Res. Commun. (1988) [Pubmed]
  11. Drug-induced anti-histone autoantibodies display two patterns of reactivity with substructures of chromatin. Burlingame, R.W., Rubin, R.L. J. Clin. Invest. (1991) [Pubmed]
  12. A low-electrophoretic-mobility H1 histone subfraction from Kirkman-Robbins hamster hepatoma. Graczyk, G.M., Bartkowiak, J.K., Plucienniczak, A., Hrabec, E.L., Panusz, T. Cancer Res. (1981) [Pubmed]
  13. The human CL100 gene encodes a Tyr/Thr-protein phosphatase which potently and specifically inactivates MAP kinase and suppresses its activation by oncogenic ras in Xenopus oocyte extracts. Alessi, D.R., Smythe, C., Keyse, S.M. Oncogene (1993) [Pubmed]
  14. Histone H1 phosphorylation occurs site-specifically during interphase and mitosis: identification of a novel phosphorylation site on histone H1. Sarg, B., Helliger, W., Talasz, H., Förg, B., Lindner, H.H. J. Biol. Chem. (2006) [Pubmed]
  15. All known human H1 histone genes except the H1(0) gene are clustered on chromosome 6. Albig, W., Drabent, B., Kunz, J., Kalff-Suske, M., Grzeschik, K.H., Doenecke, D. Genomics (1993) [Pubmed]
  16. The N-terminal peptide of the Kaposi's sarcoma-associated herpesvirus (KSHV)-cyclin determines substrate specificity. Kaldis, P. J. Biol. Chem. (2005) [Pubmed]
  17. Characterization of the H1.5 gene completes the set of human H1 subtype genes. Albig, W., Meergans, T., Doenecke, D. Gene (1997) [Pubmed]
  18. Varied expression patterns of human H1 histone genes in different cell lines. Meergans, T., Albig, W., Doenecke, D. DNA Cell Biol. (1997) [Pubmed]
  19. Characterization of phosphorylation sites on histone H1 isoforms by tandem mass spectrometry. Garcia, B.A., Busby, S.A., Barber, C.M., Shabanowitz, J., Allis, C.D., Hunt, D.F. J. Proteome Res. (2004) [Pubmed]
  20. The human H1 histone gene FNC16 is functionally expressed in proliferating HeLa S3 cells and is down-regulated during terminal differentiation in HL60 cells. Collar, D.G., Wright, K.L., van Wijnen, A.J., Ramsey, A.L., Lian, J., Stein, J.L., Stein, G.S. J. Biol. Chem. (1988) [Pubmed]
  21. Characterization of sequence variations in human histone H1.2 and H1.4 subtypes. Sarg, B., Gréen, A., Söderkvist, P., Helliger, W., Rundquist, I., Lindner, H.H. FEBS J. (2005) [Pubmed]
  22. p40MO15, a cdc2-related protein kinase involved in negative regulation of meiotic maturation of Xenopus oocytes. Shuttleworth, J., Godfrey, R., Colman, A. EMBO J. (1990) [Pubmed]
  23. Cyclin A potentiates maturation-promoting factor activation in the early Xenopus embryo via inhibition of the tyrosine kinase that phosphorylates cdc2. Devault, A., Fesquet, D., Cavadore, J.C., Garrigues, A.M., Labbé, J.C., Lorca, T., Picard, A., Philippe, M., Dorée, M. J. Cell Biol. (1992) [Pubmed]
  24. The dynamic mobility of histone H1 is regulated by cyclin/CDK phosphorylation. Contreras, A., Hale, T.K., Stenoien, D.L., Rosen, J.M., Mancini, M.A., Herrera, R.E. Mol. Cell. Biol. (2003) [Pubmed]
  25. Reconstitution of cyclin-dependent cdc2 and cdk2 kinase activities in vitro. Pan, Z.Q., Hurwitz, J. J. Biol. Chem. (1993) [Pubmed]
  26. Cyclin-dependent kinase-2 (Cdk2) forms an inactive complex with cyclin D1 since Cdk2 associated with cyclin D1 is not phosphorylated by Cdk7-cyclin-H. Higashi, H., Suzuki-Takahashi, I., Saitoh, S., Segawa, K., Taya, Y., Okuyama, A., Nishimura, S., Kitagawa, M. Eur. J. Biochem. (1996) [Pubmed]
  27. Increased expression of cyclin D2 during multiple states of growth arrest in primary and established cells. Meyyappan, M., Wong, H., Hull, C., Riabowol, K.T. Mol. Cell. Biol. (1998) [Pubmed]
  28. Differential regulation of p34cdc2 and p33cdk2 by transforming growth factor-beta 1 in murine mammary epithelial cells. Fautsch, M.P., Eblen, S.T., Anders, R.A., Burnette, R.J., Leof, E.B. J. Cell. Biochem. (1995) [Pubmed]
  29. The cyclin encoded by Kaposi's sarcoma-associated herpesvirus stimulates cdk6 to phosphorylate the retinoblastoma protein and histone H1. Godden-Kent, D., Talbot, S.J., Boshoff, C., Chang, Y., Moore, P., Weiss, R.A., Mittnacht, S. J. Virol. (1997) [Pubmed]
  30. The cyclin box and C-terminus of cyclins A and E specify CDK activation and substrate specificity. Horton, L.E., Templeton, D.J. Oncogene (1997) [Pubmed]
  31. Expression of cyclin E in resting and activated B-chronic lymphocytic leukaemia cells: cyclin E/cdk2 as a potential therapeutic target. Decker, T., Hipp, S., Hahntow, I., Schneller, F., Peschel, C. Br. J. Haematol. (2004) [Pubmed]
  32. The human and mouse replication-dependent histone genes. Marzluff, W.F., Gongidi, P., Woods, K.R., Jin, J., Maltais, L.J. Genomics (2002) [Pubmed]
  33. Human histone gene organization: nonregular arrangement within a large cluster. Albig, W., Kioschis, P., Poustka, A., Meergans, K., Doenecke, D. Genomics (1997) [Pubmed]
  34. Association of proliferating cell nuclear antigen with cyclin-dependent kinases and cyclins in normal and transformed human T lymphocytes. Szepesi, A., Gelfand, E.W., Lucas, J.J. Blood (1994) [Pubmed]
  35. Centrosome-targeting region of CG-NAP causes centrosome amplification by recruiting cyclin E-cdk2 complex. Nishimura, T., Takahashi, M., Kim, H.S., Mukai, H., Ono, Y. Genes Cells (2005) [Pubmed]
  36. Role of a distal promoter element in the S-phase control of the human H1.2 histone gene transcription. Eilers, A., Bouterfa, H., Triebe, S., Doenecke, D. Eur. J. Biochem. (1994) [Pubmed]
  37. The metaphase scaffold is helically folded: sister chromatids have predominantly opposite helical handedness. Boy de la Tour, E., Laemmli, U.K. Cell (1988) [Pubmed]
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