High fractional occupancy of a tandem Maf recognition element and its role in long-range β-globin gene regulation

Jared R. Stees, Mir A. Hossain, Tomoki Sunose, Yasushi Kudo, Carolina E. Pardo, Nancy H. Nabilsi, Russell P. Darst, Rosha Poudyal, Kazuhiko Igarashi, Suming Huang, Michael P. Kladde, Jörg Bungert

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Enhancers and promoters assemble protein complexes that ultimately regulate the recruitment and activity of RNA polymerases. Previous work has shown that at least some enhancers form stable protein complexes, leading to the formation of enhanceosomes. We analyzed protein-DNA interactions in the murine β-globin gene locus using the methyltransferase accessibility protocol for individual templates (MAPit). The data show that a tandem Maf recognition element (MARE) in locus control region (LCR) hypersensitive site 2 (HS2) reveals a remarkably high degree of occupancy during differentiation of mouse erythroleukemia cells. Most of the other transcription factor binding sites in LCR HS2 or in the adult β-globin gene promoter regions exhibit low fractional occupancy, suggesting highly dynamic protein-DNA interactions. Targeting of an artificial zinc finger DNA-binding domain (ZF-DBD) to the HS2 tandem MARE caused a reduction in the association of MARE-binding proteins and transcription complexes at LCR HS2 and the adult βmajor-globin gene promoter but did not affect expression of the βminor-globin gene. The data demonstrate that a stable MARE-associated footprint in LCR HS2 is important for the recruitment of transcription complexes to the adult βmajor-globin gene promoter during erythroid cell differentiation.

Original languageEnglish (US)
Pages (from-to)238-250
Number of pages13
JournalMolecular and cellular biology
Volume36
Issue number2
DOIs
StatePublished - Jan 1 2016

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Locus Control Region
Globins
Genes
DNA
Proteins
Personnel Selection
Leukemia, Erythroblastic, Acute
Erythroid Cells
Zinc Fingers
Methyltransferases
DNA-Directed RNA Polymerases
Genetic Promoter Regions
Cell Differentiation
Carrier Proteins
Transcription Factors
Binding Sites

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

Cite this

Stees, J. R., Hossain, M. A., Sunose, T., Kudo, Y., Pardo, C. E., Nabilsi, N. H., ... Bungert, J. (2016). High fractional occupancy of a tandem Maf recognition element and its role in long-range β-globin gene regulation. Molecular and cellular biology, 36(2), 238-250. https://doi.org/10.1128/MCB.00723-15
Stees, Jared R. ; Hossain, Mir A. ; Sunose, Tomoki ; Kudo, Yasushi ; Pardo, Carolina E. ; Nabilsi, Nancy H. ; Darst, Russell P. ; Poudyal, Rosha ; Igarashi, Kazuhiko ; Huang, Suming ; Kladde, Michael P. ; Bungert, Jörg. / High fractional occupancy of a tandem Maf recognition element and its role in long-range β-globin gene regulation. In: Molecular and cellular biology. 2016 ; Vol. 36, No. 2. pp. 238-250.
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Stees, JR, Hossain, MA, Sunose, T, Kudo, Y, Pardo, CE, Nabilsi, NH, Darst, RP, Poudyal, R, Igarashi, K, Huang, S, Kladde, MP & Bungert, J 2016, 'High fractional occupancy of a tandem Maf recognition element and its role in long-range β-globin gene regulation', Molecular and cellular biology, vol. 36, no. 2, pp. 238-250. https://doi.org/10.1128/MCB.00723-15

High fractional occupancy of a tandem Maf recognition element and its role in long-range β-globin gene regulation. / Stees, Jared R.; Hossain, Mir A.; Sunose, Tomoki; Kudo, Yasushi; Pardo, Carolina E.; Nabilsi, Nancy H.; Darst, Russell P.; Poudyal, Rosha; Igarashi, Kazuhiko; Huang, Suming; Kladde, Michael P.; Bungert, Jörg.

In: Molecular and cellular biology, Vol. 36, No. 2, 01.01.2016, p. 238-250.

Research output: Contribution to journalArticle

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T1 - High fractional occupancy of a tandem Maf recognition element and its role in long-range β-globin gene regulation

AU - Stees, Jared R.

AU - Hossain, Mir A.

AU - Sunose, Tomoki

AU - Kudo, Yasushi

AU - Pardo, Carolina E.

AU - Nabilsi, Nancy H.

AU - Darst, Russell P.

AU - Poudyal, Rosha

AU - Igarashi, Kazuhiko

AU - Huang, Suming

AU - Kladde, Michael P.

AU - Bungert, Jörg

PY - 2016/1/1

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N2 - Enhancers and promoters assemble protein complexes that ultimately regulate the recruitment and activity of RNA polymerases. Previous work has shown that at least some enhancers form stable protein complexes, leading to the formation of enhanceosomes. We analyzed protein-DNA interactions in the murine β-globin gene locus using the methyltransferase accessibility protocol for individual templates (MAPit). The data show that a tandem Maf recognition element (MARE) in locus control region (LCR) hypersensitive site 2 (HS2) reveals a remarkably high degree of occupancy during differentiation of mouse erythroleukemia cells. Most of the other transcription factor binding sites in LCR HS2 or in the adult β-globin gene promoter regions exhibit low fractional occupancy, suggesting highly dynamic protein-DNA interactions. Targeting of an artificial zinc finger DNA-binding domain (ZF-DBD) to the HS2 tandem MARE caused a reduction in the association of MARE-binding proteins and transcription complexes at LCR HS2 and the adult βmajor-globin gene promoter but did not affect expression of the βminor-globin gene. The data demonstrate that a stable MARE-associated footprint in LCR HS2 is important for the recruitment of transcription complexes to the adult βmajor-globin gene promoter during erythroid cell differentiation.

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