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Molecular and Cellular Biology, July 2006, p. 5096-5105, Vol. 26, No. 13
0270-7306/06/$08.00+0     doi:10.1128/MCB.02454-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Active Chromatin Hub of the Mouse {alpha}-Globin Locus Forms in a Transcription Factory of Clustered Housekeeping Genes

Guo-Ling Zhou,{dagger} Li Xin,{dagger} Wei Song, Li-Jun Di, Guang Liu, Xue-Song Wu, De-Pei Liu,* and Chih-Chuan Liang

National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, People's Republic of China

Received 22 December 2005/ Returned for modification 24 January 2006/ Accepted 19 April 2006

RNA polymerases can be shared by a particular group of genes in a transcription "factory" in nuclei, where transcription may be coordinated in concert with the distribution of coexpressed genes in higher-eukaryote genomes. Moreover, gene expression can be modulated by regulatory elements working over a long distance. Here, we compared the conformation of a 130-kb chromatin region containing the mouse {alpha}-globin cluster and their flanking housekeeping genes in 14.5-day-postcoitum fetal liver and brain cells. The analysis of chromatin conformation showed that the active {alpha}1 and {alpha}2 globin genes and upstream regulatory elements are in close spatial proximity, indicating that looping may function in the transcriptional regulation of the mouse {alpha}-globin cluster. In fetal liver cells, the active {alpha}1 and {alpha}2 genes, but not the inactive {zeta} gene, colocalize with neighboring housekeeping genes C16orf33, C16orf8, MPG, and C16orf35. This is in sharp contrast with the mouse {alpha}-globin genes in nonexpressing cells, which are separated from the congregated housekeeping genes. A comparison of RNA polymerase II (Pol II) occupancies showed that active {alpha}1 and {alpha}2 gene promoters have a much higher RNA Pol II enrichment in liver than in brain. The RNA Pol II occupancy at the {zeta} gene promoter, which is specifically repressed during development, is much lower than that at the {alpha}1 and {alpha}2 promoters. Thus, the mouse {alpha}-globin gene cluster may be regulated through moving in or out active globin gene promoters and regulatory elements of a preexisting transcription factory in the nucleus, which is maintained by the flanking clustered housekeeping genes, to activate or inactivate {alpha}-globin gene expression.

* Corresponding author. Mailing address: National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, People’s Republic of China. Phone: 86 10 65296415. Fax: 86 10 65105093. E-mail: liudp{at}pumc.edu.cn.

{dagger} These authors contributed equally to this work.

Molecular and Cellular Biology, July 2006, p. 5096-5105, Vol. 26, No. 13
0270-7306/06/$08.00+0     doi:10.1128/MCB.02454-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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