Recruitment of transcription complexes to the β-globin locus control region and transcription of hypersensitive site 3 prior to erythroid differentiation of murine embryonic stem cells

Abstract

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 β-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 β-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 ε- and adult β-globin genes. These results are consistent with the hypothesis that activation of the β-globin gene locus is initiated by protein complexes recruited to the LCR. © 2006 FEBS.