Published in: Molecular Cell, vol 17, no. 3, pp. 453-462  (4 February 2005),
http://www.molecule.org/content/article/abstract?uid=PIIS1097276505010154


"Proximity among Distant Regulatory Elements at the b-Globin Locus Requires GATA-1 and FOG-1".

Christopher R. Vakoc 1, 3, Danielle L. Letting 1, 3, Nele Gheldof  2, Tomoyuki Sawado 4, M.A. Bender 5, Mark Groudine 4, Mitchell J. Weiss 1, 3, Job Dekker 2, and Gerd A. Blobel 1, 3,

1 Division of Hematology, The Children's Hospital of Philadelphia, Philadelphia, PA 19104 USA
2 Program in Gene Function and Expression, Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605 USA
3 University of Pennsylvania School of Medicine, Philadelphia, PA 19104 USA
4 Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Department of Radiation Oncology, University of Washington School of Medicine, Seattle, WA 98195 USA
5 Division of Clinical Research, Fred Hutchinson Cancer Research Center, Department of Pediatrics, University of Washington School of Medicine, Seattle, WA 98195 USA

Correspondence:
Gerd A. Blobel:   (215) 590-3988 (phone):   (215) 590-4834 (fax)
E-mail:   blobel@email.chop.edu


Abstract:

Recent evidence suggests that long-range enhancers and gene promoters are in close proximity, which might
reflect the formation of chromatin loops. Here, we examined the mechanism for DNA looping at the b-globin
locus. By using chromosome conformation capture (3C), we show that the hematopoietic transcription factor
GATA-1 and its cofactor FOG-1 are required for the physical interaction between the b-globin locus control
region (LCR) and the b-major globin promoter. Kinetic studies reveal that GATA-1-induced loop formation
correlates with the onset of b-globin transcription and occurs independently of new protein synthesis. GATA-1
occupies the b-major globin promoter normally in fetal liver erythroblasts from mice lacking the LCR,
suggesting that GATA-1 binding to the promoter and LCR are independent events that occur prior to loop
formation. Together, these data demonstrate that GATA-1 and FOG-1 are essential anchors for a
tissue-specific chromatin loop, providing general insights into long-range enhancer function.


Additional References:

1. Frenster JH, and Hovsepian JA, "Ultrastructure  of Closed Loops within Euchromatin of Isolated Lymphocyte Nuclei", Molecular Biology of the Cell, vol. 15, suppl., p. 450a (November, 2004).

2. Chambeyron S,  and Bickmore WA, "Chromatin decondensation and nuclear reorganization of the HoxB locus upon induction of transcription",Genes & Development, vol. 18: no. 10, pp. 1119-1130 (May 15, 2004).

3. Frenster JH, "Ultrastructural Continuity Between Active and Repressed Chromatin", Nature vol. 205: no. 4978, pp. 1341-1342 (March 27, 1965).

4. Frenster JH, Allfrey VG, and Mirsky AE, "Metabolism and Morphology of Ribonucleoprotein Particles from the Cell Nucleus of Lymphocytes", Proc. Natl. Acad. Sci. U.S.A. vol. 46: no. 4, pp. 432-444 (April, 1960).

5. Frenster JH, Allfrey VG, and Mirsky AE, "Repressed and Active Chromatin Isolated from Interphase Lymphocytes", Proc. Natl. Acad. Sci., U.S.A. vol. 50, no. 6, pp. 1026-1032 (December, 1963).

6. Parada LA, McQueen PG,  and Misteli T, "Tissue-specific spatial organization of genomes", Genome Biology, vol. 5, no. 7, r44 (June 21, 2004).

7. Hovsepian JA, and Frenster JH, "Euchromatin as an Extensile Force within Mammalian Cell Nuclei", Molec. Biol. Cell, vol. 14, supp. p. 93a (November, 2003).

8a. Frenster JH, Nakatsu SL, and Masek MA, "Ultrastructural Probes of DNA Templates within Human Bone Marrow and Lymph Node Cells", in: "Advances in Cell and Molecular Biology", vol. 3, pp. 1-19 (1974), ed. DuPraw EJ, New York: Academic Press.

8b. Frenster JH, "Ultrastructure and Function of Heterochromatin and Euchromatin", in: "The Cell Nucleus", vol. 1, pp. 565-580, (1974), (Busch H, ed.), New York, Academic Press.

9. Frenster JH, Papalian MM, Masek MA and Frenster JA, "Electron Microscopic Analysis of Lymph Node Cellular Activity in Hodgkin's Disease", Journal of the National Cancer Institute, Vol. 63, pp. 331-335, Aug. 1979.

10. Volpi EV, Chevret E, Jones T, Vatcheva R, Williamson J, Beck S, Campbell RD, Goldsworthy M, Powis SH, Ragoussis J, Trowsdale J, and Sheer D, "Large-scale chromatin organization of the major histocompatibility complex and other regions of human chromosome 6 and its response to interferon in interphase nuclei", J. Cell Sci., vol. 113, no. 9, pp. 1565-1576 (2000).

11. Fransz P, de Jong JH, Lysak M, Castiglione MR, and Schubert I, " Interphase chromosomes in Arabidopsis are organized as well defined chromocenters from which euchromatin loops emanate", Proc. Natl. Acad. Sci., U.S.A., vol. 99, no. 22, pp. 14584-14589 (October 29, 2002).

12. O'Sullivan JM, Tan-Wong SM, Morillon A, Lee B, Coles J, Mellor J, and Proudfoot NJ, "Gene loops juxtapose promoters and terminators in yeast", Nature Genetics, vol. 36, no. 9, pp. 1014-1018 (September, 2004).

13. Osborne CS, Chakalova L, Brown KE, Carter D, Horton A, Debrand E, Goyenechea B, Mitchell JA, Lopes S, Reik W, and Fraser P, "Active genes dynamically colocalize to shared sites of ongoing transcription".

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euchromatin: "the most active portion of the genome within the cell nucleus".