tailieunhanh - Báo cáo khoa học: Recruitment of transcription complexes to the b-globin locus control region and transcription of hypersensitive site 3 prior to erythroid differentiation of murine embryonic stem cells

Eukaryotic chromosomal DNA is densely packaged in the nucleus and organized into discrete domains of active and inactive chromatin. Gene loci that are activated during the process of cell differentiation undergo changes that result in modifications of specific histone tail residues and in loosening of chromatin structure. Theb-globin genes are expressed exclusively in eryth-roid cells. | iFEBS Journal Recruitment of transcription complexes to the 0-globin locus control region and transcription of hypersensitive site 3 prior to erythroid differentiation of murine embryonic stem cells Padraic P. Levings Zhuo Zhou Karen F. Vieira Valerie J. Crusselle-Davis and Jorg Bungert Department of Biochemistry and Molecular Biology University of Florida Center for Mammalian Genetics Shands Cancer Center PowellGene Therapy Center Gainesville Florida USA Keywords differentiation globin genes locus control region RNA polymerase II transcription Correspondence J. Bungert Department of Biochemistry and Molecular Biology College of Medicine University of Florida 1600 SW Archer Road PO Box 100245 Gainesville Florida 32610 USA Fax 1 352 3922953 Tel 1 352 3920121 E-mail jbungert@ Received 23 August 2005 revised 28 November 2005 accepted 16 December 2005 doi Eukaryotic chromosomal DNA is densely packaged in the nucleus and organized into discrete domains of active and inactive chromatin. Gene loci that are activated during the process of cell differentiation undergo changes that result in modifications of specific histone tail residues and in loosening of chromatin structure. The b-globin genes are expressed exclusively in erythroid cells. High-level expression of these genes is mediated by a locus control region LCR a powerful DNA regulatory element composed of several DNase I hypersensitive HS sites and located far upstream of the b-globin genes. Here we show that RNA polymerase II and specific histone modifications that mark transcriptionally active chromatin domains are associated with the LCR core elements HS2 and HS3 in murine embryonic stem cells prior to differentiation along the erythroid lineage. At this stage HS3 is abundantly transcribed. After in vitro differentiation RNA Polymerase II can also be detected at the embryonic e- and adult b-globin genes. These results are consistent with the hypothesis that activation of .