据12月4日的《科学》（Science）杂志报道说，一种被称作BCL11A 的特殊基因会通过抑制伽马球蛋白基因的表达而发挥作用，而伽马球蛋白对人类发育时的血液健康是必须的。这个发现很重要，因为BCL11A 蛋白可能会为镰刀细胞性贫血及其它的血液病提供一种干预的标靶。伽马或倍塔球蛋白对通过血流来运输氧气是必需的，其生产通常发生在胎儿发育的时候，之后其表达被下调，而此时成人变异版的倍塔球蛋白的表达开始出现。
这一球蛋白“基因转换”在健康人中是足够的，但是当遗传缺陷中断了倍塔球蛋白生产时就会发生像镰刀样贫血等血液疾病。在这种情况下，胎儿版的伽马球蛋白可作为替代物来工作，但它的基因在正常的情况下已经通过基因转换的过程而被关闭了。Vijay Sankaran及其同事发现，BCL11A表达在成人红细胞中的下调会导致胎儿伽马球蛋白表达的增加。因此他们提出，当倍塔球蛋白的生产发生故障的时候，BCL11A可能可以用来重新激活伽马球蛋白的生产。（生物谷Bioon.com）
生物谷推荐原始出处：
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.
