DNA methylation and chromatin structure regulate PU. 1 Expression

Lakshmi Amaravadi, Michael Klemsz

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

Knockout studies have shown that PU.1 is required for the normal development of many blood cell lineages, yet overexpression of this transcription factor in erythroid cells can lead to erythroleukemia. Thus, how the tissue-specific expression of PU.1 is regulated is important to our understanding of hematopoiesis. In this study, we showed that B and macrophage cell lines expressing PU.1 contained DNase I-hypersensitive sites in intron 1 and were hypomethylated at three MspI sites flanking exon 1. Results from studies using several T-cell lines suggested that the pattern of methylation changed as these cells matured. A pre-T cell line that expresses PU.1 contained DNase I-hypersensitive sites in intron 1 and was also hypomethylated at both MspI sites. Other immature T-cell lines had methylated at least one of the MspI sites and displayed no hypersensitive sites. Mature T-cell lines had a methylation pattern more similar to that of fibroblasts. Treatment of an immature T-cell line with 5-azacytidine resulted in the expression of PU.1 transcripts. These data suggest that the tissue-specific expression of PU.1 is controlled by chromatin structure and DNA methylation and that this may be a mechanism used to shut off PU.1 expression in specific cell lineages during hematopoiesis.

Original languageEnglish
Pages (from-to)875-884
Number of pages10
JournalDNA and Cell Biology
Volume18
Issue number12
DOIs
StatePublished - Dec 1999

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DNA Methylation
Chromatin
Cell Line
T-Lymphocytes
Deoxyribonuclease I
Hematopoiesis
Cell Lineage
Introns
Methylation
Azacitidine
Leukemia, Erythroblastic, Acute
Erythroid Cells
Exons
Blood Cells
Transcription Factors
Fibroblasts
Macrophages

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

DNA methylation and chromatin structure regulate PU. 1 Expression. / Amaravadi, Lakshmi; Klemsz, Michael.

In: DNA and Cell Biology, Vol. 18, No. 12, 12.1999, p. 875-884.

Research output: Contribution to journalArticle

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