BCL11A represses HBG transcription in K562 cells

被引：49

作者：

Chen, Zhiyi ^{[1
]}

Luo, Hong-yuan ^{[1
]}

Steinberg, Martin H. ^{[1
,2
]}

Chui, David H. K. ^{[1
,2
]}

机构：

[1] Boston Univ, Sch Med, Dept Med, Div Hematol Oncol,Ctr Excellence Sickle Cell Dis, Boston, MA 02118 USA

[2] Boston Univ, Sch Med, Dept Pathol & Lab Med, Boston, MA 02118 USA

来源：

BLOOD CELLS MOLECULES AND DISEASES | 2009年 / 42卷 / 02期

关键词：

BETA-THALASSEMIA; FETAL-HEMOGLOBIN; GENE-EXPRESSION; F-CELLS; PROMOTER; COMPLEX; BINDING; PROTEIN; HERITABILITY; UPSTREAM;

D O I：

10.1016/j.bcmd.2008.12.003

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

BCL11A on chromosome 2p16 was recently shown to be a major quantitative trait locus for Hb F level and F-cell number in several populations with or without beta-hemoglobinopathy. We now show that BCL11A isoforms are expressed in K562 cells. Butyrate induction of HBG globin production in K562 is associated with reduced BCL11A. Conversely, augmented expression of BCL11A in K562 cells through transfection of BCL11A expression vector results in more than 50% reduction of HBG promoter transcription activity. This transcription repression can be abrogated by sodium butyrate. BCL11A binds to GGCCGG motif in nucleotide -56 to -51 on the HBG proximal promoter. Together, these data are consistent with BCL11A being able to bind to a core motif in the HBG proximal promoter, recruit and interact with partners to form a repression complex, leading to deacetylation of histones and down-regulation of the HBG transcription. (c) 2008 Elsevier Inc. All rights reserved.

引用

页码：144 / 149

页数：6

共 19 条

[1] COUP-TF (chicken ovalbumin upstream promoter transcription factor)-interacting protein 1 (CTIP1) is a sequence-specific DNA binding protein [J].