KLF3 Regulates Muscle-Specific Gene Expression and Synergizes with Serum Response Factor on KLF Binding Sites

Himeda, Charis L.; Ranish, Jeffrey A.; Pearson, Richard; Crossley, Merlin; Hauschka, Stephen D.

doi:10.1128/mcb.00302-10

Cited by 54 publications

(52 citation statements)

References 68 publications

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“…KLF3 has also recently been identified as a transcriptional regulator of skeletal muscle differentiation (28). This report showed that KLF3 expression increases during skeletal myocyte differentiation and a proteomics screen found KLF3 enriched at the muscle creatine kinase promoter (MCK).…”

Section: Klf3 and Muscle Cell Biologymentioning

confidence: 87%

“…Further understanding will be dependent on defining the FHL3-binding motif and examining changes in gene expression in KLF3 null cell lines, rescued with KLF3 protein in which this site has been mutated. The high level of expression of FHL3 in skeletal and cardiac muscle and recent reports linking KLF3 with muscle cell growth and differentiation (28,29), hints that common targets may be found in this tissue. Apart from the conserved CtBP-binding motif, KLF3 shares little N-terminal homology with KLF8 and KLF12, suggesting that the association with FHL3 may not be shared with KLF3's most closely related family members.…”

Section: Protein Partners Of Klf3mentioning

confidence: 99%

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The mammalian zinc finger transcription factor Krüppel‐like factor 3 (KLF3/BKLF)

2011

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KLF3 is a member of the Krüppel‐like factor (KLF) family of transcription factors. These proteins are classified by the presence of three C‐terminal C2H2 zinc fingers that allow sequence‐specific binding to CACCC boxes and GC‐rich motifs found in the promoters, enhancers, and other control regions of target genes. KLFs have diverse biological roles, regulating proliferation, differentiation, and apoptosis in many tissues throughout development. KLF3 is a transcriptional repressor that binds the cofactor C‐terminal binding protein, which in turn recruits a large repressor complex to mediate transcriptional silencing. In addition to an understanding of the molecular mechanisms that allow KLF3 to regulate the expression of its target genes, the biological roles of this transcription factor are now being defined. In agreement with the widespread expression pattern of this transcription factor, it is becoming clear that KLF3 is an important regulator of several biological processes, including adipogenesis, erythropoiesis, and B cell development. © 2011 IUBMB IUBMB Life, 63(2): 86–93, 2011

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Section: Klf3 and Muscle Cell Biologymentioning

confidence: 87%

Section: Protein Partners Of Klf3mentioning

confidence: 99%

The mammalian zinc finger transcription factor Krüppel‐like factor 3 (KLF3/BKLF)

2011

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“…in certain contexts it can function as an activator (15,16). Its hematopoietic role has not been fully characterized, although it is known to be a direct target gene of the erythroid factor Klf1 (17).…”

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confidence: 99%

Impaired B Cell Development in the Absence of Krüppel-like Factor 3

Vũ

Gatto

Turner

et al. 2011

The Journal of Immunology

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Krüppel-like factor 3 (Klf3) is a member of the Klf family of transcription factors. Klfs are widely expressed and have diverse roles in development and differentiation. In this study, we examine the function of Klf3 in B cell development by studying B lymphopoiesis in a Klf3 knockout mouse model. We show that B cell differentiation is significantly impaired in the bone marrow, spleen, and peritoneal cavity of Klf3 null mice and confirm that the defects are cell autonomous. In the bone marrow, there is a reduction in immature B cells, whereas recirculating mature cells are noticeably increased. Immunohistology of the spleen reveals a poorly structured marginal zone (MZ) that may in part be caused by deregulation of adhesion molecules on MZ B cells. In the peritoneal cavity, there are significant defects in B1 B cell development. We also report that the loss of Klf3 in MZ B cells is associated with reduced BCR signaling strength and an impaired ability to respond to LPS stimulation. Finally, we show increased expression of a number of Klf genes in Klf3 null B cells, suggesting that a Klf regulatory network may exist in B cells.

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“…The transcription factor SRF physically associates and synergizes with KLF3, thereby working as a transactivation complex, as shown for a muscle-specific target gene (12). Furthermore, mice in which SRF was deleted in B cells show a loss of MZ B cells (63), a phenotype shared with KLF3-deficient mice (7,9).…”

Section: Srf Is Irrelevant Both For Klf3 Repressing B 7 and Driving Mmentioning

confidence: 85%

“…Indeed, KLF3 has been shown to interact with the common transcriptional corepressors C-terminal binding protein 2 (CtBP2) and four and a half LIM domain protein 3 (FHL3) (8,10,11). A further KLF3-interacting transcription factor is serum response factor (SRF), as identified in muscle cells (12). Thus, KLF3 may act exclusively in concert with other transcriptional regulators.…”

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confidence: 99%

Leukocyte β7 Integrin Targeted by Krüppel-like Factors

Alles

Turchinovich

Zhang

et al. 2014

The Journal of Immunology

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Constitutive expression of Krüppel-like factor 3 (KLF3, BKLF) increases marginal zone (MZ) B cell numbers, a phenotype shared with mice lacking KLF2. Ablation of KLF3, known to interact with serum response factor (SRF), or SRF itself, results in fewer MZ B cells. It is unknown how these functional equivalences result. In this study, it is shown that KLF3 acts as transcriptional repressor for the leukocyte-specific integrin β7 (Itgb7, Ly69) by binding to the β7 promoter, as revealed by chromatin immunoprecipitation. KLF2 overexpression antagonizes this repression and also binds the β7 promoter, indicating that these factors may compete for target sequence(s). Whereas β7 is identified as direct KLF target, its repression by KLF3 is not connected to the MZ B cell increase because β7-deficient mice have a normal complement of these and the KLF3-driven increase still occurs when β7 is deleted. Despite this, KLF3 overexpression abolishes lymphocyte homing to Peyer’s patches, much like β7 deficiency does. Furthermore, KLF3 expression alone overcomes the MZ B cell deficiency when SRF is absent. SRF is also dispensable for the KLF3-mediated repression of β7. Thus, despite the shared phenotype of KLF3 and SRF-deficient mice, cooperation of these factors appears neither relevant for the formation of MZ B cells nor for the regulation of β7. Finally, a potent negative regulatory feedback loop limiting KLF3 expression is shown in this study, mediated by KLF3 directly repressing its own gene promoter. In summary, KLFs use regulatory circuits to steer lymphocyte maturation and homing and directly control leukocyte integrin expression.

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KLF3 Regulates Muscle-Specific Gene Expression and Synergizes with Serum Response Factor on KLF Binding Sites

Cited by 54 publications

References 68 publications

The mammalian zinc finger transcription factor Krüppel‐like factor 3 (KLF3/BKLF)

The mammalian zinc finger transcription factor Krüppel‐like factor 3 (KLF3/BKLF)

Impaired B Cell Development in the Absence of Krüppel-like Factor 3

Leukocyte β7 Integrin Targeted by Krüppel-like Factors

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