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The structure of the Klf4 DNA-binding domain links to self-renewal and macrophage differentiation

Schuetz, Anja, Nana, Didier, Rose, Charlotte, Zocher, Georg, Milanovic, Maja, Koenigsmann, Jessica, Blasig, Rosel, Heinemann, Udo, Carstanjen, Dirk·2011·Cellular and Molecular Life Sciences
DOI 10.1007/s00018-010-0618-x
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Abstract

Krueppel-like factor 4 (Klf4) belongs to the Sp/Klf family of zinc-finger transcription factors and is indispensable for terminal maturation of epithelial tissues. Furthermore, it is part of a small set of proteins that are used to generate pluripotent embryonic stem cells from differentiated tissues. Herein, we describe that a Klf4 zinc-finger domain mutant induces self-renewal and block of maturation, while wild-type Klf4 induces terminal macrophage differentiation. Moreover, we present the crystal structure of the zinc-finger domain of Klf4 bound to its target DNA, revealing that primarily the two C-terminal zinc-finger motifs are required for site specificity. Lack of those two zinc fingers leads to deficiency of Klf4 to induce macrophage differentiation. The first zinc finger, on the other hand, inhibits the otherwise cryptic self-renewal and block of differentiation activity of Klf4. Our data show that impairing the DNA binding could potentially contribute to a monocytic leukemia.

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  • KLF4 contains both activator and repressor domains, conferring a dual function during cell differentiation.

    “KLF4 is a transcription factor containing both activator and repressor domains, conferring a dual function during cell differentiation 52 (Fig. 1c).”

    From Mechanisms, pathways and strategies for rejuvenation through epigenetic reprogramming (2023) · cites this paper as [52]

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Metadata

Authors
Schuetz, A., Nana, D., Rose, C., Zocher, G., Milanovic, M., Koenigsmann, J., Blasig, R., Heinemann, U., & Carstanjen, D.
Venue
Cellular and Molecular Life Sciences
Publisher
Springer Science and Business Media LLC
Published
2011-02-03
Volume
68
Issue
18
Pages
3121-3131
ISSN
  • 1420-682X
  • 1420-9071
DOI
10.1007/s00018-010-0618-x
Cited by
84
References
1
Language
en
Licence
www.springer.com/tdm (tdm)

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