Biopolym. Cell. 2011; 27(5):364-368.
Dynamic nature of active chromatin hubs
1Gavrilov A. A., 1Philonenko E. S., 1Iarovaia O. V., 1Razin S. V.
  1. Institute of Gene Biology, Russian Academy of Sciences
    34/5, Vavilova Str., Moscow, Russian Federation, 119334

Abstract

Aim. In order to get more information about organization of active chromatin hubs and their role in the regulation of gene transcription we have studied the spatial organization of the α-globin gene domain in cultured chicken erythroblasts. Methods. The chromosome conformation capture (3C) protocol was employed to analyze the 3D configuration of the chicken α-globin gene domain. Results. We have demonstrated that in the same cell population the chicken domain of α-globin gene may be organized in two different active chromatin hubs. One of them appears essential for the activation of the α-globin gene expression while the other – for the activation of TMEM8 gene which constitutes a part of the α-globin gene domain in chicken, but not in human and other mammals. Importantly, two regulatory elements participate in the formation of both active chromatin hubs. Conclusions. The assembly of the same genomic area into two alternative chromatin hubs which share some regulatory elements suggests that active chromatin hubs are dynamic rather than static, and that regulatory elements may shuttle between different chromatin hubs.
Keywords: active chromatin hub, globin gene, genomic domain, chromosome conformation capture

References

[1] Wijgerde M., Grosveld F., Fraser P. Transcription complex stability and chromatin dynamics in vivo Nature 1995 377, N 6546 P. 209–213.
[2] Gribnau J., de Boer E., Trimborn T., Wijgerde M., Milot E., Grosveld F., Fraser P. Chromatin interaction mechanism of transcriptional control in vivo EMBO J 1998 17, N 20 P. 6020–6027.
[3] Palstra R. J., de Laat W., Grosveld F. Beta-globin regulation and long-range interactions Adv. Genet 2008 61 P. 107– 142.
[4] de Laat W., Klous P., Kooren J., Noordermeer D., Palstra R. J., Simonis M., Splinter E., Grosveld F. Three-dimensional organization of gene expression in erythroid cells Curr. Top. Dev. Biol 2008 82 P. 117–139.
[5] Dekker J., Rippe K., Dekker M., Kleckner N. Capturing chromosome conformation Science 2002 295, N 5558 P. 1306– 1311.
[6] Kooren J., Palstra R. J., Klous P., Splinter E., von Lindern M., Grosveld F., de Laat W. Beta-globin active chromatin Hub formation in differentiating erythroid cells and in p45 NF-E2 knock-out mice J. Biol. Chem 2007 282, N 22 P. 16544– 16552.
[7] de Laat W., Grosveld F. Spatial organization of gene expression: the active chromatin hub Chromosome Res 2003 11, N 5 P. 447–459.
[8] Tolhuis B., Palstra R. J., Splinter E., Grosveld F., de Laat W. Looping and interaction between hypersensitive sites in the active beta-globin locus Mol. Cell 2002 10, N 6 P. 1453–1465.
[9] Beug H., von Kirchbach A., Doderlein G., Conscience J. F., Graf T. Chicken hematopoietic cells transformed by seven strains of defective avian leukemia viruses display three distinct phenotypes of differentiation Cell 1979 18, N 2 P. 375–390.
[10] Nicolas R. H., Partington G., Major G. N., Smith B., Carne A. F., Huskisson N., Goodwin G. Induction of differentiation of avian erythroblastosis virus-transformed erythroblasts by the protein kinase inhibitor H7: analysis of the transcription factor EF1 Cell Growth Differ 1991 2, N 3 P. 129–135.
[11] Splinter E., Grosveld F., de Laat W. 3C technology: analyzing the spatial organization of genomic loci in vivo Methods Enzymol 2004 375 P. 493–507.
[12] Gavrilov A. A., Razin S. V. Spatial configuration of the chicken alpha-globin gene domain: immature and active chromatin hubs Nucleic Acids Res 2008 36, N 14 P. 4629–4640.
[13] Filonenko E. S., Gavrilov A. A., Razin S. V., Iarovaia O. V. Expansion of the functional domain of chicken alpha-globin genes Genetika 2010 46, N 9 P. 1164–1167.
[14] Beug H., Doederlein G., Freudenstein C., Graf T. Erythroblast cell lines transformed by a temperature-sensitive mutant of avian erythroblastosis virus: a model system to study erythroid differentiation in vitro J. Cell Physiol. Suppl 1982 1 P. 195–207.
[15] Razin S. V., Rynditch A., Borunova V., Ioudinkova E., Smalko V., Scherrer K. The 33 kb transcript of the chicken alpha-globin gene domain is part of the nuclear matrix J. Cell Biochem 2004 92, N 3 P. 445–457.
[16] Liu Z., Garrard W. T. Long-range interactions between three transcriptional enhancers, active Vkappa gene promoters, and a 3' boundary sequence spanning 46 kilobases Mol. Cell Biol 2005 25, N 8 P. 3220–3231.
[17] Zhou G. L., Xin L., Song W., Di L. J., Liu G., Wu X. S., Liu D. P., Liang C. C. Active chromatin hub of the mouse alpha-globin locus forms in a transcription factory of clustered housekeeping genes Mol. Cell Biol 2006 26, N 13 P. 5096–5105.