脊椎动物胚胎到胎儿的转变，以为血液中的伽马球蛋白编码的基因之间一个发育开关为特征，而球蛋白基因表达的发育调控方式在小鼠与人类之间则有所不同。一项涉及将人类贝塔球蛋白位点连同周围DNA的100个“千碱基对”插入小鼠基因组的实验表明，BCL11A基因是造成这种调控差别的原因。
BCLA11A蛋白是人类伽马球蛋白表达的一个抑制因子，是以前通过整个基因组范围的关联研究被识别出来的。这一关于在演化过程中所发生的基因表达的一种改变的实例，也为了解在临床上具有重要意义的人类血红蛋白从胎儿到成年之转变的机制提供了新线索。（生物谷Bioon.com）
生物谷推荐原始出处：
Nature 460, 1093-1097 (27 August 2009) | doi:10.1038/nature08243
Developmental and species-divergent globin switching are driven by BCL11A
Vijay G. Sankaran1,8, Jian Xu1,2,8, Tobias Ragoczy3, Gregory C. Ippolito4, Carl R. Walkley1,9, Shanna D. Maika4, Yuko Fujiwara1,2, Masafumi Ito5, Mark Groudine3,6, M. A. Bender3,7, Philip W. Tucker4 & Stuart H. Orkin1,2
1 Division of Hematology/Oncology, Children's Hospital Boston and Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Stem Cell Institute, Harvard Medical School, Boston, Massachusetts 02115, USA
2 Howard Hughes Medical Institute, Boston, Massachusetts 02115, USA
3 Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA
4 Institute for Cellular and Molecular Biology, The University of Texas at Austin, Austin, Texas 78712, USA
5 Department of Pathology, Japanese Red Cross, Nagoya First Hospital, Nagoya, Japan
6 Department of Radiation Oncology, and,
7 Department of Pediatrics, University of Washington, Seattle, Washington 98195, USA
8 These authors contributed equally to this work.
9 Present address: St Vincent's Institute of Medical Research, Fitzroy, Victoria 3065, Australia.
The contribution of changes in cis-regulatory elements or trans-acting factors to interspecies differences in gene expression is not well understood. The mammalian -globin loci have served as a model for gene regulation during development. Transgenic mice containing the human -globin locus, consisting of the linked embryonic (), fetal () and adult () genes, have been used as a system to investigate the temporal switch from fetal to adult haemoglobin, as occurs in humans. Here we show that the human -globin (HBG) genes in these mice behave as murine embryonic globin genes, revealing a limitation of the model and demonstrating that critical differences in the trans-acting milieu have arisen during mammalian evolution. We show that the expression of BCL11A, a repressor of human -globin expression identified by genome-wide association studies, differs between mouse and human. Developmental silencing of the mouse embryonic globin and human -globin genes fails to occur in mice in the absence of BCL11A. Thus, BCL11A is a critical mediator of species-divergent globin switching. By comparing the ontogeny of -globin gene regulation in mice and humans, we have shown that alterations in the expression of a trans-acting factor constitute a critical driver of gene expression changes during evolution.
