4.6 Article

Identification and Functional Analysis of the Regulatory Elements in the pHSPA6 Promoter

Journal

GENES
Volume 13, Issue 2, Pages -

Publisher

MDPI
DOI: 10.3390/genes13020189

Keywords

HSP70; pig; pHSPA6; heat shock element; stress response

Funding

  1. National Key Research and Development Program of China Stem Cell and Translational Research [2019YFA0110702]
  2. Youth Program of the National Natural Science Foundation of China [31902229]
  3. Program for JLU Science and Technology Innovative Research Team [2017TD-28]

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Research on porcine HSPA6 gene reveals its sensitivity to heat stress and other stimuli, with heat shock elements and a conserved region identified in the promoter region through precise gene editing. Downregulation of pHSPA6 significantly impacts key members of the HSP family, indicating potential implications for gene regulation mechanisms and drug target selection.
Functional and expressional research of heat shock protein A6 (HSPA6) suggests that the gene is of great value for neurodegenerative diseases, biosensors, cancer, etc. Based on the important value of pigs in agriculture and biomedicine and to advance knowledge of this little-studied HSPA member, the stress-sensitive sites in porcine HSPA6 (pHSPA6) were investigated following different stresses. Here, two heat shock elements (HSEs) and a conserved region (CR) were identified in the pHSPA6 promoter by a CRISPR/Cas9-mediated precise gene editing strategy. Gene expression data showed that sequence disruption of these regions could significantly reduce the expression of pHSPA6 under heat stress. Stimulation studies indicated that these regions responded not only to heat stress but also to copper sulfate, MG132, and curcumin. Further mechanism studies showed that downregulated pHSPA6 could significantly affect some important members of the HSP family that are involved in HSP40, HSP70, and HSP90. Overall, our results provide a new approach for investigating gene expression and regulation that may contribute to gene regulatory mechanisms, drug target selection, and breeding stock selection.

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