據(jù)12月4日的《科學(xué)》（Science）雜志報(bào)道說,，一種被稱作BCL11A 的特殊基因會通過抑制伽馬球蛋白基因的表達(dá)而發(fā)揮作用，而伽馬球蛋白對人類發(fā)育時的血液健康是必須的,。這個發(fā)現(xiàn)很重要,，因?yàn)锽CL11A 蛋白可能會為鐮刀細(xì)胞性貧血及其它的血液病提供一種干預(yù)的標(biāo)靶。伽馬或倍塔球蛋白對通過血流來運(yùn)輸氧氣是必需的,，其生產(chǎn)通常發(fā)生在胎兒發(fā)育的時候,，之后其表達(dá)被下調(diào)，而此時成人變異版的倍塔球蛋白的表達(dá)開始出現(xiàn),。

這一球蛋白“基因轉(zhuǎn)換”在健康人中是足夠的,，但是當(dāng)遺傳缺陷中斷了倍塔球蛋白生產(chǎn)時就會發(fā)生像鐮刀樣貧血等血液疾病。在這種情況下,，胎兒版的伽馬球蛋白可作為替代物來工作,，但它的基因在正常的情況下已經(jīng)通過基因轉(zhuǎn)換的過程而被關(guān)閉了,。Vijay Sankaran及其同事發(fā)現(xiàn)，BCL11A表達(dá)在成人紅細(xì)胞中的下調(diào)會導(dǎo)致胎兒伽馬球蛋白表達(dá)的增加,。因此他們提出,，當(dāng)倍塔球蛋白的生產(chǎn)發(fā)生故障的時候，BCL11A可能可以用來重新激活伽馬球蛋白的生產(chǎn),。（生物谷Bioon.com）

生物谷推薦原始出處：

Science,，DOI: 10.1126/science.1165409，Vijay G. Sankaran,，Stuart H. Orkin

Human Fetal Hemoglobin Expression Is Regulated by the Developmental Stage-Specific Repressor BCL11A

Vijay G. Sankaran 1, Tobias F. Menne 2, Jian Xu 2, Thomas E. Akie 2, Guillaume Lettre 3, Ben Van Handel 4, Hanna K.A. Mikkola 4, Joel N. Hirschhorn 3, Alan B. Cantor 2, Stuart H. Orkin 5*

1 Division of Hematology/ Oncology, Children's Hospital Boston, Harvard Stem Cell Institute, Harvard Medical School, Boston, MA 02115, USA.; Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
2 Division of Hematology/ Oncology, Children's Hospital Boston, Harvard Stem Cell Institute, Harvard Medical School, Boston, MA 02115, USA.
3 Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.; Divisions of Genetics and Endocrinology and Program in Genomics, Children’s Hospital Boston, Boston, MA 02115, USA.
4 Department of Molecular, Cell, and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA
5 Division of Hematology/ Oncology, Children's Hospital Boston, Harvard Stem Cell Institute, Harvard Medical School, Boston, MA 02115, USA.; Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.; Howard Hughes Medical Institute, Boston, MA 02115, USA.

Differences in the amount of fetal hemoglobin (HbF) that persists into adulthood affect the severity of sickle cell disease and the β-thalassemia syndromes. Genetic association studies have identified sequence variants in the geneBCL11A that influence HbF levels. Here, we examine BCL11A as a potential regulator of HbF expression. The high-HbF BCL11A genotype is associated with reduced BCL11A expression. Moreover, abundant expression of full-length forms of BCL11A is developmentally restricted to adult erythroid cells. Down-regulation of BCL11A expression in primary adult erythroid cells leads to robust HbF expression. Consistent with a direct role of BCL11A in globin gene regulation, we find that BCL11A occupies several discrete sites in the β-globin gene cluster. BCL11A emerges as atherapeutic target for reactivation of HbF in β-hemoglobin disorders.