Runx1 transcription factor is involved in the regulation of KAP5 gene expression in human hair follicles

Soma, Tsutomu; Ishimatsu‐Tsuji, Yumiko; Tajima, Masahiro; Kishimoto, Jiro

doi:10.1016/j.jdermsci.2005.12.012

Cited by 5 publications

(7 citation statements)

References 10 publications

(13 reference statements)

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“…A recent study in human hair follicles showed that Runx1 is expressed in the epithelial hair follicle -in the matrix as well as in the HS, ORS and the IRS (Soma et al, 2006). Our report reveals that this factor is active in the epithelial as well as in the dermal compartment of the mouse hair follicle.…”

Section: Resultssupporting

confidence: 66%

“…Runx1 expression in the distal part of the hair matrix and in their daughter hair cuticle and cortex cells, as well as the localization of Runx1 to the nail matrix, may implicate this gene as a regulator of the keratinization program of terminal differentiation, occurring in both appendages. Recent finding of Runx1-mediated up-regulation of keratin-associated protein 5 (KAP5) transcription in vitro (Soma et al, 2006) gives credence to this notion.…”

Section: Resultsmentioning

confidence: 94%

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Dynamic expression of Runx1 in skin affects hair structure

Raveh

Cohen

Levanon

et al. 2006

Mechanisms of Development

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The three mammalian Runx transcription factors, some of which are known to be involved in human genetic diseases and cancer, are pivotal players in embryo development and function as key regulators of cell fate determination and organogenesis. Here, we report the expression of Runx1 during the development of hair and other skin appendages in the mouse and describe the effect of Runx1 on the structural hair output. In hair follicles, where the three Runx proteins are expressed, Runx1 expression is most prominent in both mesenchymal and epithelial compartments. The epithelial expression includes the hair keratin forming layers of the hair shaft and the bulge, where interestingly, Runx1 is co-expressed with keratin 15, a putative hair follicle stem cell marker. In the hair mesenchyme, during early stages of hair morphogenesis, Runx1 is expressed in a discrete dermal sub-epithelial layer, while at later stages it is found in a hair cycle dependent pattern in the dermal papilla. To elucidate the function of Runx1 in the hair follicle we have generated a Runx1 epidermal conditional knockout and found that the mutant mice display a remarkable structural deformation of the zigzag hair type. The data delineate Runx1 as a novel specific marker of several hair follicle cell types and sheds light on its role in hair morphogenesis and differentiation.

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Section: Resultssupporting

confidence: 66%

Section: Resultsmentioning

confidence: 94%

Dynamic expression of Runx1 in skin affects hair structure

Raveh

Cohen

Levanon

et al. 2006

Mechanisms of Development

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“…20 We therefore investigated whether RUNX1 was also expressed in human interfollicular epidermis, using a RUNX1-specific antibody on sections of normal human skin (Figure 1). As previously described, a strong RUNX1 expression was observed in cell nuclei from both the outer root sheath and the inner root sheath of human anagen hair follicles (Figures 1a and b).…”

Section: Resultsmentioning

confidence: 99%

“…17, 18, 19 In human skin, RUNX1 is also highly expressed in hair follicles and involved in KAP5 regulation, a keratin-associated protein expressed in the cuticle layer of anagen hair follicles. 20 …”

mentioning

confidence: 99%

Functional interplay between p63 and p53 controls RUNX1 function in the transition from proliferation to differentiation in human keratinocytes

et al. 2012

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The interfollicular epidermis is continuously renewed, thanks to a regulated balance between proliferation and differentiation. The ΔNp63 transcription factor has a key role in the control of this process. It has been shown that ΔNp63 directly regulates Runt-related transcription factor 1 (RUNX1) transcription factor expression in mouse keratinocytes. The present study showed for the first time that RUNX1 is expressed in normal human interfollicular epidermis and that its expression is tightly regulated during the transition from proliferation to differentiation. It demonstrated that ΔNp63 directly binds two different RUNX1 regulatory DNA sequences and modulates RUNX1 expression differentially in proliferative or differentiated human keratinocytes. It also showed that the regulation of RUNX1 expression by ΔNp63 is dependent on p53 and that this coregulation relies on differential binding and activation of RUNX1 regulatory sequences by ΔNp63 and p53. We also found that RUNX1 inhibits keratinocyte proliferation and activates directly the expression of KRT1, a critical actor in early keratinocyte differentiation. Finally, we described that RUNX1 expression, similar to ΔNp63 and p53, was strongly expressed and downregulated in basal cell carcinomas and squamous cell carcinomas respectively. Taken together, these data shed light on the importance of tight control of the functional interplay between ΔNp63 and p53 in regulating RUNX1 transcription factor expression for proper regulation of interfollicular epidermal homeostasis.

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“…All the findings acquired in mice begged the question of the role of Runx1 in normal and diseased human skin. Importantly, when Runx1 expression was compared in mice and men similar patterns emerged in the HF at different hair cycle stages [Raveh et al, 2006; Soma et al, 2006; Osorio et al, 2008; Hoi et al, 2010]. Human Runx1 expression partially overlaps with that of human keratin associated protein 5 (hKAP5.1).…”

Section: Runx1 In Hair Follicle Stem Cellsmentioning

confidence: 99%

New insights into the role of Runx1 in epithelial stem cell biology and pathology

Scheitz

Tumbar

2013

J of Cellular Biochemistry

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The transcription factor Runx1 has been studied in leukemia and blood for decades, but recently it has been also implicated in epithelial biology and pathology. Particularly in mouse skin Runx1 modulates Wnt signaling levels thereby regulating timely induction of hair follicle specification, proper maturation of the emerging adult hair follicle stem cells in embryogenesis, and timely stem cell (SC) activation during adult homeostasis. Moreover, Runx1 acts as a tumor promoter in mouse skin squamous tumor formation and maintenance, likely by repressing p21 and promoting Stat3 activation. Similarly, Runx1 is essential for oral epithelium tumorigenesis mediated in mice by Ras, and for growth of three kinds of human epithelial cancer cells. In contrast, Runx1 has a tumor suppressor function in the mouse intestine and shows tumor subtype specific behavior in human breast cancer. Multiple studies revealed Runx1 SNPs to be associated with human cancers and autoimmune disease. With this information as background, the field is poised for functional and mechanistic studies to elucidate the role of Runx1 in formation and/or progression of epithelial-based human disease.

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Runx1 transcription factor is involved in the regulation of KAP5 gene expression in human hair follicles

Cited by 5 publications

References 10 publications

Dynamic expression of Runx1 in skin affects hair structure

Dynamic expression of Runx1 in skin affects hair structure

Functional interplay between p63 and p53 controls RUNX1 function in the transition from proliferation to differentiation in human keratinocytes

New insights into the role of Runx1 in epithelial stem cell biology and pathology

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