We have continued our studies of chromatin structure in the neighborhood of expressed genes. The globin gene family in chicken erythroid cells serves as a model system in which it is possible to study the mechanisms associated with regulation of the individual members of the family during erythroid development. We have extended our studies of stage- specific erythroid expression in the alpha-globin gene family to the chicken embryonic alpha(pi)-globin gene, and shown that changes in the concentrations of three trans-acting factors that interact and that vary in concentration during development may account for much of the stage-specific expression. We have also extended studies of the structure and function of the general erythroid-specific factor GATA-1. We have continued investigation of the effects of chromatin structure on gene expression. We have investigated the structure and genesis of locus control regions (LCRs) in the human and chicken beta-globin loci. We have also identified a DNA sequence element far upstream in the chicken beta-globin locus that can serve as an insulator to block the action of an LCR/enhancer on a promoter. The insulating element functions both in human erythroid cell lines and in Drosophila, and may be part of a complex marking the boundary between chromatin domains. Work also continues on the effects of supercoiling on chromatin structure, and on the mechanism by which RNA polymerase transcribes through chromatin. We find that transcription through nucleosome cores involves an intramolecular transfer in which the core is displaced backward on the DNA without leaving the template.

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Gaszner, Miklos; Felsenfeld, Gary (2006) Insulators: exploiting transcriptional and epigenetic mechanisms. Nat Rev Genet 7:703-13
Jin, Chunyuan; Felsenfeld, Gary (2006) Distribution of histone H3.3 in hematopoietic cell lineages. Proc Natl Acad Sci U S A 103:574-9
Huang, Suming; Litt, Michael; Felsenfeld, Gary (2005) Methylation of histone H4 by arginine methyltransferase PRMT1 is essential in vivo for many subsequent histone modifications. Genes Dev 19:1885-93
Studitsky, Vasily M; Walter, Wendy; Kireeva, Maria et al. (2004) Chromatin remodeling by RNA polymerases. Trends Biochem Sci 29:127-35
Yusufzai, Timur M; Tagami, Hideaki; Nakatani, Yoshihiro et al. (2004) CTCF tethers an insulator to subnuclear sites, suggesting shared insulator mechanisms across species. Mol Cell 13:291-8
Yusufzai, Timur M; Felsenfeld, Gary (2004) The 5'-HS4 chicken beta-globin insulator is a CTCF-dependent nuclear matrix-associated element. Proc Natl Acad Sci U S A 101:8620-4
Felsenfeld, G; Burgess-Beusse, B; Farrell, C et al. (2004) Chromatin boundaries and chromatin domains. Cold Spring Harb Symp Quant Biol 69:245-50
Felsenfeld, Gary (2004) Obituary. Robert Simpson. Nucleic Acids Res 32:2975-6
Magdinier, Frederique; Yusufzai, Timur M; Felsenfeld, Gary (2004) Both CTCF-dependent and -independent insulators are found between the mouse T cell receptor alpha and Dad1 genes. J Biol Chem 279:25381-9
Ghirlando, Rodolfo; Litt, Michael D; Prioleau, Marie-Noelle et al. (2004) Physical properties of a genomic condensed chromatin fragment. J Mol Biol 336:597-605

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