Intergenic Transcription in the Human {beta}-Globin Gene Cluster

doi:10.1128/MCB.21.19.6507-6514.2001

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Molecular and Cellular Biology, October 2001, p. 6507-6514, Vol. 21, No. 19
0270-7306/01/$04.00+0 DOI: 10.1128/MCB.21.19.6507-6514.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Intergenic Transcription in the Human $beta$ -Globin Gene Cluster

Kathryn E. Plant, Samantha J. E. Routledge, and Nick J. Proudfoot^*

Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, United Kingdom

Received 29 January 2001/Returned for modification 9 May 2001/Accepted 2 July 2001

Our previous studies on nascent transcription across the human $beta$ -globin gene cluster revealed the presence of intergenic transcriptsin addition to the expected genic transcripts. We now show thattranscription into the $beta$ -globin locus control region (LCR) beginswithin an ERV9 endogenous retroviral long terminal repeat upstreamof DNase I hypersensitive site 5. However, in a transgenic mouse,which has the human $beta$ -globin LCR but lacks the ERV9 LTR, transcriptionbegins upstream of the transgenic locus. We postulate that inthis transgenic mouse nearby endogenous mouse promoters are activatedby the LCR. Intergenic transcription is also detected across thewhole transgenic globin gene locus independently of the stageof erythroid development. Intergenic transcription in the $beta$ -globincluster is erythroid specific; however, it can be induced in nonerythroidcells by several means: by transinduction with a plasmid transcribingpart of the cluster, by exogenous addition of transcription factors,and by treatment with the histone deacetylase inhibitor trichostatinA.

^* Corresponding author. Mailing address: Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, UnitedKingdom. Phone: 44-(0)1865 275566. Fax: 44-(0)1865 275556. E-mail:nicholas.proudfoot{at}path.ox.ac.uk.

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Intergenic Transcription in the Human -Globin Gene Cluster

Intergenic Transcription in the Human $beta$ -Globin Gene Cluster