title: Identification of novel candidate genes for globin regulation in erythroid cells containing large deletions of the human beta-globin gene cluster.
abstract: The genetic mechanisms underlying the continued expression of the gamma-globin genes during the adult stage in deletional hereditary persistence of fetal hemoglobin (HPFH) and deltabeta-thalassemias are not completely understood. Herein, we investigated the possible involvement of transcription factors, using the suppression subtractive hybridization (SSH) method as an initial screen to identify differentially expressed transcripts in reticulocytes from a normal and a HPFH-2 subject. Some of the detectable transcripts may participate in globin gene regulation. Quantitative real-time PCR (qRT-PCR) experiments confirmed the downregulation of ZHX2, a transcriptional repressor, in two HPFH-2 subjects and in a carrier of the Sicilian deltabeta-thalassemia trait. The chromatin remodeling factors ARID1B and TSPYL1 had a very similar pattern of expression with an incremental increase in HPFH and decreased expression in deltabeta-thalassemia. These differences suggest a mechanism to explain the heterocellular and pancellular distribution of fetal hemoglobin in deltabeta-thalassemia and deletional HPFH, respectively. Interestingly, alpha-globin mRNA levels were decreased, similar to beta-globin in all reticulocyte samples analyzed.
authors.affiliation: Institute of Medical and Biological Sciences, Federal University of Alagoas, Maceió, AL, Brazil. tgandrade@ig.com.br
authors.forename: Tiago Gomes
authors.initials: TG
authors.lastname: de Andrade
authors.forename: Kenneth R
authors.initials: KR
authors.lastname: Peterson
authors.forename: Anderson F
authors.initials: AF
authors.lastname: Cunha
authors.forename: Luciana Sarmento
authors.initials: LS
authors.lastname: Moreira
authors.forename: André
authors.initials: A
authors.lastname: Fattori
authors.forename: Sara T O
authors.initials: ST
authors.lastname: Saad
authors.forename: Fernando Ferreira
authors.initials: FF
authors.lastname: Costa
mesh_terms: D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D041905:Erythroid Cells / Q000378:metabolism*; D005260:Female; D005319:Fetal Hemoglobin / Q000235:genetics; D020869:Gene Expression Profiling; D015723:Gene Library; D005914:Globins / Q000235:genetics* / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D051741:Kruppel-Like Transcription Factors; D008297:Male; D005810:Multigene Family; D009687:Nuclear Proteins; D009693:Nucleic Acid Hybridization / Q000379:methods; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012680:Sensitivity and Specificity; D017384:Sequence Deletion; D013789:Thalassemia / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: C497837:ARID1B protein, human; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D051741:Kruppel-Like Transcription Factors; D009687:Nuclear Proteins; D011506:Proteins; D012333:RNA, Messenger; C510183:TSPYL1 protein, human; D014157:Transcription Factors; C476826:ZHX2 protein, human; C451412:ZNF84 protein, human; D005914:Globins; D005319:Fetal Hemoglobin