The National Institute of Diabetes & Digestive & Kidney Diseases

The laboratory studies how enhancers activate transcription during development and differentiation, with particular interest in the role played by chromatin structure in this process. The model system employed is the family of human globin genes that are expressed in a tissue specific and developmentally regulated fashion under the influence of the beta-globin locus control region enhancer (LCR). Studies are being carried out to map the precise changes in nucleosome organization that accompany gene activation, and to understand the role of transcription factors, and transcription and replication per se. Other studies using mutagenesis, and in vitro and in vivo ligation approaches, are addressing the extent to which the interaction of a promoter and an enhancer involves close contact. Another area of interest is in establishing which transcription factors and mediators are actually bound in vivo to a transcribing gene promoter or enhancer by using cross linking and immunoprecipitation. The goal of these studies is to understand the complex interplay between nuclear genes and their modulators. Understanding the role of chromatin structure in gene regulation is important to gene therapy efforts.

Sripichai O, Kiefer CM, Bhanu NV, Tanno T, Noh SJ, Goh SH, Russell JE, Rognerud CL, Ou CN, Oneal PA, Meier ER, Gantt NM, Byrnes C, Lee YT, Dean A, Miller JL (2009) Cytokine mediated increases in fetal hemoglobin are associated with globin gene histone modification and transcription factor reprogramming. Blood, in press (e-pub ahead of print). [PubMed]

Bhatia H, Hallock JL, Dutta A, Karkashon S, Sterner LS, Miyazaki T, Dean A, Little JA (2009) Short-chain fatty acid-mediated effects on erythropoiesis in primary definitive erythroid cells. Blood 113:6440-8. [PubMed] [Full Text via PubMed Central]

Kim SI, Bultman SJ, Kiefer CM, Dean A, Bresnick EH (2009) BRG1 requirement for long-range interaction of a locus control region with a downstream promoter. Proc Natl Acad Sci U S A 106:2259-64. [PubMed] [Full Text via PubMed Central]

Dean A, Fiering S (2009) Epigenetic Gene Regulation-Lessons from Globin, in Epigenomics. Springer (New York, NY, USA), pp. 283-299.

Kiefer CM, Hou C, Little JA, Dean A (2008) Epigenetics of beta-globin gene regulation. Mutat Res 647:68-76. [PubMed] [Full Text via PubMed Central]

Hou C, Zhao H, Tanimoto K, Dean A (2008) CTCF-dependent enhancer-blocking by alternative chromatin loop formation. Proc Natl Acad Sci U S A 105:20398-403. [PubMed] [Full Text via PubMed Central]

Song, SH, Hou, C, Dean, A (2007) A positive role for NLI/Ldb1 in long range beta-globin locus control region function Molecular Cell 28: 810-822.

Kim A, Zhao H, Ifrim I, Dean A (2007) Beta-globin intergenic transcription and histone acetylation dependent on an enhancer. Mol Cell Biol 27: 2980-6. [Full Text/Abstract]

3. Kim A, Kiefer CM, Dean A (2007) Distinctive signatures of histone methylation in transcribed coding and noncoding human beta-globin sequences. Mol Cell Biol 27: 1271-1279. [Full Text/Abstract]

Kim A, Song SH, Brand M, Dean A (2007) Nucleosome and transcription activator antagonism at human {beta}-globin locus control region DNase I hypersensitive sites. Nucleic Acids Res, 35: 5831-5838. [Full Text/Abstract]

Zhao H, Kim A, Song SH, Dean A (2006) Enhancer blocking by chicken beta-globin 5''-HS4: role of enhancer strength and insulator nucleosome depletion. J Biol Chem 281: 30573-80. [Full Text/Abstract]

Dean A (2006) On a chromosome far, far away: LCRs and gene expression. Trends Genet 22: 38-45. [Full Text/Abstract]

Zhao H, Dean A (2005) Organizing the genome: enhancers and insulators. Biochem Cell Biol 83: 516-24. [Full Text/Abstract]

Zhao H, Dean A (2004) An insulator blocks spreading of histone acetylation and interferes with RNA polymerase II transfer between an enhancer and gene. Nucleic Acids Res 32: 4903-19. [Full Text/Abstract]

Dean A (2004) Chromatin remodelling and the interaction between enhancers and promoters in the beta-globin locus. Brief Funct Genomic Proteomic 2: 344-54. [Full Text/Abstract]

Kim A, Dean A (2004) Developmental stage differences in chromatin subdomains of the beta-globin locus. Proc Natl Acad Sci U S A 101: 7028-33. [Full Text/Abstract]

Kim A Dean A (2003) A human globin enhancer causes both discrete and widespread alterations in chromatin structure. Mol Cell Biol 23: 8099-109. [Full Text/Abstract]

Gui CY Dean A (2003) A major role for the TATA box in recruitment of chromatin modifying complexes to a globin gene promoter. Proc Natl Acad Sci U S A 100: 7009-14. [Full Text/Abstract]

Jackson DA McDowell JC Dean A (2003) Beta-globin locus control region HS2 and HS3 interact structurally and functionally. Nucleic Acids Res 31: 1180-90. [Full Text/Abstract]