Krüppel-like transcription factors: A functional family

Pearson, Richard; Fleetwood, J; Eaton, Sally A.; Crossley, Merlin; Bao, Shisan

doi:10.1016/j.biocel.2007.07.018

Cited by 354 publications

(290 citation statements)

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“…To date, 17 family members have been described (1) and all share homology with the zinc finger DNA-binding domain of the Drosophila segmentation factor Krüppel (2). KLFs have a highly conserved C-terminal DNA-binding domain consisting of three classical C2H2 zinc fingers that contact CACCC box motifs and GC-rich sequences in the promoters and enhancers of target genes (3). The N-terminal region of family members is more varied thus allowing interaction with diverse coregulator proteins.…”

Section: Introductionmentioning

confidence: 99%

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: Introductionmentioning

confidence: 99%

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

2011

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“…They are zinc finger containing TFs named after the segmentation gene product Kruppel originally identified in Drosophila melanogaster, in which it plays an essential role in embryogenesis (13). In mammals they constitute a large family of factors containing at least seventeen members that bind to a CACCC or CGCCC DNA motif (14,15). KLF's have pleiotropic functions that both enhance and inhibit transcription (16), and through competition for binding to their target sequences, they can mutually antagonize each other (15,17).…”

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confidence: 99%

“…In mammals they constitute a large family of factors containing at least seventeen members that bind to a CACCC or CGCCC DNA motif (14,15). KLF's have pleiotropic functions that both enhance and inhibit transcription (16), and through competition for binding to their target sequences, they can mutually antagonize each other (15,17). They have a wide range of functions in regulating cell cycle, apoptosis, and differentiation (15).…”

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“…KLF's have pleiotropic functions that both enhance and inhibit transcription (16), and through competition for binding to their target sequences, they can mutually antagonize each other (15,17). They have a wide range of functions in regulating cell cycle, apoptosis, and differentiation (15). KLFs affect expression of proproliferative genes such as E, D and A type cyclins.…”

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KLF15 negatively regulates estrogen-induced epithelial cell proliferation by inhibition of DNA replication licensing

Ray

Pollard²

2012

Proc. Natl. Acad. Sci. U.S.A.

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In the epithelial compartment of the uterus, estradiol-17β (E 2 ) induces cell proliferation while progesterone (P 4 ) inhibits this response and causes differentiation of the cells. In this study, we identified the mechanism whereby E 2 and P 4 reciprocally regulate the expression of minichromosome maintenance (MCM)-2, a protein that is an essential component of the hexameric MCM-2 to 7 complex required for DNA synthesis initiation. We show in the uterine epithelium that Kruppel-like transcription (KLF) factors, KLF 4 and 15, are inversely expressed; most importantly, they bind to the Mcm2 promoter under the regulation of E 2 and P 4 E 2 , respectively. After P 4 E 2 exposure and in contrast to E 2 treated mice, the Mcm2 promoter displays increased histone 3 (H3) methylation and the recruitment of histone deacetylase 1 and 3 with the concomitant deacetylation of H3. This increased methylation and decreased acetylation is associated with an inhibition of RNA polymerase II binding, indicating an inactive Mcm2 promoter following P 4 E 2 treatment. Using transient transfection assays in the Ishikawa endometrial cell line, we demonstrate that Mcm2 promoter activity is hormonally stimulated by E 2 and that KLF15 inhibits this E 2 enhanced transcription. KLF15 expression also blocks Ishikawa cell proliferation through inhibition of MCM2 protein level. Importantly, in vivo expression of KLF15 in an estrogenized uterus mimics P 4 's action by inhibiting E 2 -induced uterine epithelial MCM-2 expression and DNA synthesis. KLF15 is therefore a downstream physiological mediator of progesterone's cell cycle inhibitory action in the uterine epithelium.endometrium | implantation | menstrual cycle | endometriosis E stradiol-17β (E 2 ) and progesterone (P 4 ) directs uterine preparation for pregnancy. These hormones synthesized cyclically in humans cause a sequential series of proliferative and differentiation events in the uterine stroma and epithelium that result in the epithelium being receptive to the blastocyst for attachment and subsequent implantation (1). Despite this close control of uterine cell proliferation, aberrant proliferative conditions of the human endometrium are common. For example, endometrial polyps and endometriosis are caused by inappropriate proliferation of the uterus, while unopposed estrogen stimulation is associated with menstrual irregularities and endometrial hyperplasia/adenocarcinoma (2). Endometrial cancer is the most common female genital tract malignancy and is responsible for 6% of cancer deaths of women in the United States and more worldwide (3). However, the molecular mechanisms underlying these pathologies are still obscure, as are the molecular mechanisms involved in normal hormonal regulation of cell proliferation in the endometrium, which is essential for successful pregnancy (4).The mouse uterus provides a unique in vivo model to study the regulation of epithelial cell proliferation as the physiological actions of E 2 and P 4 E 2 can be recapitulated in ovariectomized animals by treat...

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“…KLFs consist of 17 zinc finger domain transcription factors that bind to GC-or GT-rich DNA regions to regulate transcription and thereby influence multiple biological events (20,21). KLFs are also involved in regulating stem cell selfrenewal and differentiation.…”

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confidence: 99%

Kruppel-like Factor-9 (KLF9) Inhibits Glioblastoma Stemness through Global Transcription Repression and Integrin α6 Inhibition

Ying

Tilghman

Wei

et al. 2014

Journal of Biological Chemistry

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Background: Cancer cell stemness determines tumor propagation and malignancy by poorly defined mechanisms. Results: The KLF9 transcription factor regulates cell fate and oncogenic pathways by repressing gene transcription in glioblastoma stem cells. Conclusion: KLF9 inhibits glioblastoma cell stemness and tumor growth by directly repressing genes, including ITGA6. Significance: KLF9 and its transcriptional network are potential targets for regulating cancer stem cells and glial malignancies.

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Krüppel-like transcription factors: A functional family

Cited by 354 publications

References 20 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)

KLF15 negatively regulates estrogen-induced epithelial cell proliferation by inhibition of DNA replication licensing

Kruppel-like Factor-9 (KLF9) Inhibits Glioblastoma Stemness through Global Transcription Repression and Integrin α6 Inhibition

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