# KLF14 and SREBF-1 Binding Site Associations with Orphan Receptor Promoters in Metabolic Syndrome

**Authors:** Julio Jesús Garcia-Coste, Santiago Villafaña-Rauda, Karla Aidee Aguayo-Cerón, Cruz Vargas-De-León, Rodrigo Romero-Nava

PMC · DOI: 10.3390/ijms26072849 · International Journal of Molecular Sciences · 2025-03-21

## TL;DR

This study shows that the transcription factors KLF14 and SREBF-1 are linked to the regulation of orphan receptor genes, which may influence the development of metabolic syndrome.

## Contribution

The study reveals novel associations between KLF14 and SREBF-1 binding sites and orphan receptor promoters in the context of metabolic syndrome.

## Key findings

- KLF14 and SREBF-1 binding sites in OR gene promoters are significantly associated with the total number of binding sites in the distal region.
- KLF14 shows a stronger association than SREBF-1 in regulating OR gene expression.
- Statistical models confirmed the associations and adjusted for overdispersion in the data.

## Abstract

This study investigated the relationship between the transcription factors (TFs) KLF14 and SREBF-1 and orphan receptors (ORs) in the context of metabolic syndrome (MetS). A detailed bioinformatics analysis identified a significant association between the presence of binding sites (BS) for these TFs in the promoters of ORs genes and the total number of BS in the distal region. The results suggest that KLF14 and SREBF-1 can regulate the expression of some of these genes and, in turn, can modulate the development of MetS. Although a stronger association was observed with KLF14, both factors showed a significant contribution. Additionally, the sequence similarity of KLF14 also contributed to the quantity of BS in the gene’s distal region (DR). The statistical models used, such as Poisson and negative binomial regression, confirmed these associations and allowed for the appropriate adjustment of overdispersion present in the data. However, no significant differences in receptor groups (orphan G Protein-Coupled Rereptors (oGPCRs) and G Protein-Coupled Receptors associated with MetS (GPCRs-MetS)) regarding their relationship with TFs were found. In conclusion, this study provides strong evidence of the importance of KLF14 and SREBF-1 in regulating orphan receptors genes and their participation in the development of metabolic syndrome.

## Linked entities

- **Genes:** KLF14 (KLF transcription factor 14) [NCBI Gene 136259], SREBF1 (sterol regulatory element binding transcription factor 1) [NCBI Gene 6720]
- **Diseases:** metabolic syndrome (MONDO:0000816)

## Full-text entities

- **Genes:** KLF14 (KLF transcription factor 14) [NCBI Gene 136259] {aka BTEB5}, SREBF1 (sterol regulatory element binding transcription factor 1) [NCBI Gene 6720] {aka HMD, IFAP2, SREBP1, bHLHd1}
- **Diseases:** MetS (MESH:D024821)

## Full text

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## Figures

18 figures with captions in the complete paper: https://tomesphere.com/paper/PMC11988724/full.md

## References

82 references — full list in the complete paper: https://tomesphere.com/paper/PMC11988724/full.md

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Source: https://tomesphere.com/paper/PMC11988724