脊椎動(dòng)物胚胎到胎兒的轉(zhuǎn)變,，以為血液中的伽馬球蛋白編碼的基因之間一個(gè)發(fā)育開關(guān)為特征，而球蛋白基因表達(dá)的發(fā)育調(diào)控方式在小鼠與人類之間則有所不同,。一項(xiàng)涉及將人類貝塔球蛋白位點(diǎn)連同周圍DNA的100個(gè)“千堿基對(duì)”插入小鼠基因組的實(shí)驗(yàn)表明,，BCL11A基因是造成這種調(diào)控差別的原因,。
BCLA11A蛋白是人類伽馬球蛋白表達(dá)的一個(gè)抑制因子，是以前通過(guò)整個(gè)基因組范圍的關(guān)聯(lián)研究被識(shí)別出來(lái)的,。這一關(guān)于在演化過(guò)程中所發(fā)生的基因表達(dá)的一種改變的實(shí)例，也為了解在臨床上具有重要意義的人類血紅蛋白從胎兒到成年之轉(zhuǎn)變的機(jī)制提供了新線索,。（生物谷Bioon.com）
生物谷推薦原始出處：
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.
