title: Allele-specific transcription of fetal genes in primary erythroid cell cultures from Lepore and deltabeta degrees thalassemia patients.
abstract: OBJECTIVE
  Autonomous gene silencing and gene competition by globin promoters for locus control region (LCR) function have been proposed as mechanisms in developmental regulation of beta-like genes. deltabeta degrees thalassemias are syndromes presenting an increased production of fetal hemoglobin in adult life; the majority of them are due to various deletions in beta-globin gene cluster. We studied samples from double heterozygotes for beta-thalassemia and for Lepore or Sicilian deltabeta degrees deletions, both lacking beta-promoter sequence. Our goal was to address the question of whether the allele carrying the deltabeta degrees deletion is responsible for high level of fetal hemoglobin (HbF) production.
  
  
  METHODS
  We analyzed the globin gene transcription in human erythroid cell cultures from peripheral blood stem cells, using primary transcript in situ hybridization. We performed primary erythroid cultures from patients with the following genotypes: Lepore/beta degrees 39, Sicilian deltabeta degrees /beta degrees 39, and, as controls, two thalassemia patients with nondeletional mutations (IVS1,6/IVS1,6; IVS1,6/beta degrees 39), and one normal individual.
  
  
  RESULTS
  The cells where it is possible to unambiguously assign gamma genes transcription in cis with the deletion (gamma:beta) are strongly represented with respect to the nine other combinations of gamma and beta hybridization signals. These cells are at least nine times more represented than those expressing the gamma allele in trans to the deletion.
  
  
  CONCLUSIONS
  The allele-specific transcription of fetal genes in cis with the deletion is favored in both deletional genotypes. The absence of the adult promoter may influence LCR recruitment by fetal promoter, supporting the hypothesis that competition mechanism and gene silencing can coexist in regulating human globin gene transcription.
authors.affiliation: Unità di Ricerca P. Cutino, Ematologia II, Palermo, Italy. rosalbadimarzo@virgilio.it
authors.forename: Rosalba
authors.initials: R
authors.lastname: Di Marzo
authors.forename: Santina
authors.initials: S
authors.lastname: Acuto
authors.forename: Roberta
authors.initials: R
authors.lastname: Calzolari
authors.forename: Aurelio
authors.initials: A
authors.lastname: Maggio
mesh_terms: D000483:Alleles; D002478:Cells, Cultured; D041905:Erythroid Cells / Q000378:metabolism*; D005319:Fetal Hemoglobin / Q000235:genetics*; D005786:Gene Expression Regulation; D020868:Gene Silencing; D005838:Genotype; D005914:Globins / Q000235:genetics*; D006412:Hematopoietic Stem Cells / Q000378:metabolism; D006801:Humans; D017403:In Situ Hybridization; D009154:Mutation; D011401:Promoter Regions, Genetic; D013789:Thalassemia / Q000097:blood*; D014158:Transcription, Genetic
chemical_list: D005914:Globins; D005319:Fetal Hemoglobin