Transcription of the hypersensitive site HS2 enhancer in erythroid cells

Dorothy Tuan Lo, Suming Kong, Kenneth Hu

Research output: Contribution to journalArticle

130 Citations (Scopus)

Abstract

In the human genome, the erythroid-specific hypersensitive site HS2 enhancer regulates the transcription of the downstream β-like globin genes 10-50 kilobases away. The mechanism of HS2 enhancer function is not known. The present study employs RNA protection assays to analyze the transcriptional status of the HS2 enhancer in transfected recombinant chloramphenicol acetyltransferase (CAT) plasmids. In erythroid K562 cells in which the HS2 enhancer is active, the HS2 sequence directs the synthesis of long enhancer transcripts that are initiated apparently from within the enhancer and elongated through the intervening DNA into the cis-linked CAT gene. In nonerythroid HL-60 cells in which the HS2 enhancer is inactive, long enhancer transcripts are not detectable. Splitting the HS2 enhancer between two tandem Ap1 sites abolishes the synthesis of a group of long enhancer transcripts and results in loss of enhancer function and transcriptional silencing of the cis-linked CAT gene. In directing the synthesis of RNA through the intervening DNA and the gene by a tracking and transcription mechanism, the HS2 enhancer may (i) open up the chromatin structure of a gene domain and (ii) deliver enhancer binding proteins to the promoter sequence where they may stimulate the transcription of the gene at the cap site.

Original languageEnglish (US)
Pages (from-to)11219-11223
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume89
Issue number23
DOIs
StatePublished - Dec 1 1992

Fingerprint

Erythroid Cells
Chloramphenicol O-Acetyltransferase
Genes
RNA
Globins
K562 Cells
HL-60 Cells
DNA
Human Genome
Chromatin
Carrier Proteins
Plasmids

Keywords

  • Ap1 sites
  • Enhancer function
  • Long enhancer transcripts
  • RNA protection assays

ASJC Scopus subject areas

  • General

Cite this

Transcription of the hypersensitive site HS2 enhancer in erythroid cells. / Tuan Lo, Dorothy; Kong, Suming; Hu, Kenneth.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 89, No. 23, 01.12.1992, p. 11219-11223.

Research output: Contribution to journalArticle

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