# SP1 and KROX20 Regulate the Proliferation of Dermal Papilla Cells and Target the CUX1 Gene

## TL;DR

This study identifies SP1 and KROX20 as key regulators of the CUX1 gene, which influences the proliferation of dermal papilla cells in sheep.

## Contribution

The study reveals SP1 and KROX20 as upstream transcriptional regulators of CUX1 in ovine dermal papilla cells.

## Key findings

- SP1 promotes the proliferation of dermal papilla cells.
- KROX20 inhibits the proliferation of dermal papilla cells.
- SP1 and KROX20 regulate the CUX1 gene in ovine dermal papilla cells.

## Abstract

Dermal papilla cells (DPCs) are an important cell in the hair follicle that can maintain nutrition and induce hair follicle formation. A previous study demonstrated that CUT-like homeobox 1 (CUX1) could promote the proliferation of ovine DPCs, but the upstream transcriptional regulatory mechanisms of the CUX1 gene remain largely unknown. In the present study, we aim to investigate the upstream transcriptional regulators of CUX1 to enhance our comprehension of the mechanism of the CUX1 gene in ovine DPCs. Our findings demonstrate that SP1 and KROX20 are two upstream transcriptional regulators of CUX1 and play a critical role in regulating the proliferation of ovine DPCs.

Previous studies have demonstrated that CUX1 could contribute to the proliferation of DPCs in vitro, but the upstream transcriptional regulatory mechanisms of CUX1 remain largely unknown. This study aimed to investigate the upstream transcriptional regulators of CUX1 to enhance our comprehension of the mechanism of action of the CUX1 gene in ovine DPCs. Initially, the JASPAR (2024) software was used to predict the upstream target transcription factors for the CUX1 gene. Subsequently, through RT-qPCR and a double luciferase reporter assay, the interaction between SP1, KROX20, and CUX1 was established, respectively. The results indicated that SP1 and KROX20 were two highly reliable upstream transcription regulators for the CUX1 gene. Additionally, we found that SP1 promoted the proliferation of DPCs by overexpressing SP1 in DPCs, and KROX20 inhibited the proliferation of DPCs by overexpressing KROX20 in DPCs. These findings are also consistent with the transcriptional regulation of CUX1 by SP1 and KROX20, respectively. This study suggests that the effect of DPC proliferation in vitro by CUX1 may regulated by the transcription factors SP1 and KROX20.