α-thalassemia resulting from a negative chromosomal position effect

被引:43
作者
Barbour, VM
Tufarelli, C
Sharpe, JA
Smith, ZE
Ayyub, H
Heinlein, CA
Sloane-Stanley, J
Indrak, K
Wood, WG
Higgs, DR [1 ]
机构
[1] John Radcliffe Hosp, Inst Mol Med, Mol Haematol Unit, MRC, Oxford OX3 9DU, England
[2] Fac Hosp, IP Pavlova, Dept Clin Haematol, Olomouc, Czech Republic
关键词
D O I
10.1182/blood.V96.3.800.015k11a_800_807
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
To date, all of the chromosomal deletions that cause alpha-thalassemia remove the structural alpha genes and/or their regulatory element (HS -40), A unique deletion occurs in a single family that juxtaposes a region that normally lies approximately 18-kilobase downstream of the human alpha cluster, next to a structurally normal alpha-globin gene, and silences its expression. During development, the CpG island associated with the alpha-globin promoter in the rearranged chromosome becomes densely methylated and insensitive to endonucleases, demonstrating that the normal chromatin structure around the alpha-globin gene is perturbed by this mutation and that the gene is inactivated by a negative chromosomal position effect. These findings highlight the importance of the chromosomal environment in regulating globin gene expression. (C) 2000 by The American Society of Hematology.
引用
收藏
页码:800 / 807
页数:8
相关论文
共 55 条
  • [1] Good genes in bad neighbourhoods
    Bedell, MA
    Jenkins, NA
    Copeland, NG
    [J]. NATURE GENETICS, 1996, 12 (03) : 229 - 232
  • [2] BERNET A, 1995, BLOOD, V86, P1202
  • [3] CLARK SJ, 1994, NUCLEIC ACIDS RES, V22, P2990, DOI 10.1093/nar/22.15.2990
  • [4] A ROSY FUTURE FOR HETEROCHROMATIN
    COOK, KR
    KARPEN, GH
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (12) : 5219 - 5221
  • [5] CONTRASTING EFFECTS OF ALPHA-GLOBIN AND BETA-GLOBIN REGULATORY ELEMENTS ON CHROMATIN STRUCTURE MAY BE RELATED TO THEIR DIFFERENT CHROMOSOMAL ENVIRONMENTS
    CRADDOCK, CF
    VYAS, P
    SHARPE, JA
    AYYUB, H
    WOOD, WG
    HIGGS, DR
    [J]. EMBO JOURNAL, 1995, 14 (08) : 1718 - 1726
  • [6] CHROMOSOME BANDS - FLAVORS TO SAVOUR
    CRAIG, JM
    BICKMORE, WA
    [J]. BIOESSAYS, 1993, 15 (05) : 349 - 354
  • [7] DEVLIN RH, 1990, GENETICS, V125, P129
  • [8] EBERL DF, 1993, GENETICS, V134, P277
  • [9] RANDOM ACTIVATION OF A TRANSGENE UNDER THE CONTROL OF A HYBRID HCD2 LOCUS-CONTROL REGION IG ENHANCER REGULATORY ELEMENT
    ELLIOTT, JI
    FESTENSTEIN, R
    TOLAINI, M
    KIOUSSIS, D
    [J]. EMBO JOURNAL, 1995, 14 (03) : 575 - 584
  • [10] Locus control region function and heterochromatin-induced position effect variegation
    Festenstein, R
    Tolaini, M
    Corbella, P
    Mamalaki, C
    Parrington, J
    Fox, M
    Miliou, A
    Jones, M
    Kioussis, D
    [J]. SCIENCE, 1996, 271 (5252) : 1123 - 1125