PU.1 and epigenetic signals modulate 1,25-dihydroxyvitamin D 3 and C/EBPα regulation of the human cathelicidin antimicrobial peptide gene in lung epithelial cells

Ran Wei, Puneet Dhawan, Robert A. Baiocchi, Ki Yoon Kim, Sylvia Christakos

Research output: Contribution to journalArticle

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Abstract

LL-37, the only known human cathelicidin which is encoded by the human antimicrobial peptide (CAMP) gene, plays a critical role in protection against bacterial infection. We previously demonstrated that cathelicidin is induced by 1,25-dihydroxyvitamin D 3 (1,25(OH) 2 D 3 ) in human airway epithelial cells with a resultant increase in bactericidal activity. In this study we identify key factors that co-operate with 1,25(OH) 2 D 3 in the regulation of CAMP. Our results show for the first time that PU.1, the myeloid transcription factor (which has also been identified in lung epithelial cells), co-operates with the vitamin D receptor and CCAAT/enhancer binding protein α (CEBPα) to enhance the induction of CAMP in lung epithelial cells. Our findings also indicate that enhancement of 1,25(OH) 2 D 3 regulation of CAMP by histone deacetylase inhibitors involves co-operation between acetylation and chromatin remodeling through Brahma-related gene 1 (BRG1; a component of the SWItch/sucrose nonfermentable [SWI/SNF] complex). BRG1 can be an activator or repressor depending on BRG1-associated factors. Protein arginine methyltransferase 5 (PRMT5), a methlytransferase which interacts with BRG1, represses 1,25(OH) 2 D 3 induced CAMP in part through dimethylation of H4R3. Our findings identify key mediators involved in the regulation of the CAMP gene in lung epithelial cells and suggest new approaches for therapeutic manipulation of gene expression to increase the antibacterial capability of the airway.

Original languageEnglish (US)
Pages (from-to)10345-10359
Number of pages15
JournalJournal of Cellular Physiology
Volume234
Issue number7
DOIs
StatePublished - Jul 1 2019

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Dilatation and Curettage
Epigenomics
Genes
Epithelial Cells
Lung
Protein-Arginine N-Methyltransferases
CCAAT-Enhancer-Binding Proteins
Acetylation
Calcitriol Receptors
Histone Deacetylase Inhibitors
Chromatin Assembly and Disassembly
Bacterial Infections
Gene expression
Chromatin
Sucrose
Transcription Factors
Switches
Gene Expression
Peptides
cathelicidin antimicrobial peptide

All Science Journal Classification (ASJC) codes

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

Keywords

  • 1
  • 25-dihydroxyvitamin D
  • Brahma-related gene 1
  • PU.1
  • cathelicidin
  • histone acetylation
  • protein arginine methyltransferase 5

Cite this

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title = "PU.1 and epigenetic signals modulate 1,25-dihydroxyvitamin D 3 and C/EBPα regulation of the human cathelicidin antimicrobial peptide gene in lung epithelial cells",
abstract = "LL-37, the only known human cathelicidin which is encoded by the human antimicrobial peptide (CAMP) gene, plays a critical role in protection against bacterial infection. We previously demonstrated that cathelicidin is induced by 1,25-dihydroxyvitamin D 3 (1,25(OH) 2 D 3 ) in human airway epithelial cells with a resultant increase in bactericidal activity. In this study we identify key factors that co-operate with 1,25(OH) 2 D 3 in the regulation of CAMP. Our results show for the first time that PU.1, the myeloid transcription factor (which has also been identified in lung epithelial cells), co-operates with the vitamin D receptor and CCAAT/enhancer binding protein α (CEBPα) to enhance the induction of CAMP in lung epithelial cells. Our findings also indicate that enhancement of 1,25(OH) 2 D 3 regulation of CAMP by histone deacetylase inhibitors involves co-operation between acetylation and chromatin remodeling through Brahma-related gene 1 (BRG1; a component of the SWItch/sucrose nonfermentable [SWI/SNF] complex). BRG1 can be an activator or repressor depending on BRG1-associated factors. Protein arginine methyltransferase 5 (PRMT5), a methlytransferase which interacts with BRG1, represses 1,25(OH) 2 D 3 induced CAMP in part through dimethylation of H4R3. Our findings identify key mediators involved in the regulation of the CAMP gene in lung epithelial cells and suggest new approaches for therapeutic manipulation of gene expression to increase the antibacterial capability of the airway.",
keywords = "1, 25-dihydroxyvitamin D, Brahma-related gene 1, PU.1, cathelicidin, histone acetylation, protein arginine methyltransferase 5",
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PU.1 and epigenetic signals modulate 1,25-dihydroxyvitamin D 3 and C/EBPα regulation of the human cathelicidin antimicrobial peptide gene in lung epithelial cells. / Wei, Ran; Dhawan, Puneet; Baiocchi, Robert A.; Kim, Ki Yoon; Christakos, Sylvia.

In: Journal of Cellular Physiology, Vol. 234, No. 7, 01.07.2019, p. 10345-10359.

Research output: Contribution to journalArticle

TY - JOUR

T1 - PU.1 and epigenetic signals modulate 1,25-dihydroxyvitamin D 3 and C/EBPα regulation of the human cathelicidin antimicrobial peptide gene in lung epithelial cells

AU - Wei, Ran

AU - Dhawan, Puneet

AU - Baiocchi, Robert A.

AU - Kim, Ki Yoon

AU - Christakos, Sylvia

PY - 2019/7/1

Y1 - 2019/7/1

N2 - LL-37, the only known human cathelicidin which is encoded by the human antimicrobial peptide (CAMP) gene, plays a critical role in protection against bacterial infection. We previously demonstrated that cathelicidin is induced by 1,25-dihydroxyvitamin D 3 (1,25(OH) 2 D 3 ) in human airway epithelial cells with a resultant increase in bactericidal activity. In this study we identify key factors that co-operate with 1,25(OH) 2 D 3 in the regulation of CAMP. Our results show for the first time that PU.1, the myeloid transcription factor (which has also been identified in lung epithelial cells), co-operates with the vitamin D receptor and CCAAT/enhancer binding protein α (CEBPα) to enhance the induction of CAMP in lung epithelial cells. Our findings also indicate that enhancement of 1,25(OH) 2 D 3 regulation of CAMP by histone deacetylase inhibitors involves co-operation between acetylation and chromatin remodeling through Brahma-related gene 1 (BRG1; a component of the SWItch/sucrose nonfermentable [SWI/SNF] complex). BRG1 can be an activator or repressor depending on BRG1-associated factors. Protein arginine methyltransferase 5 (PRMT5), a methlytransferase which interacts with BRG1, represses 1,25(OH) 2 D 3 induced CAMP in part through dimethylation of H4R3. Our findings identify key mediators involved in the regulation of the CAMP gene in lung epithelial cells and suggest new approaches for therapeutic manipulation of gene expression to increase the antibacterial capability of the airway.

AB - LL-37, the only known human cathelicidin which is encoded by the human antimicrobial peptide (CAMP) gene, plays a critical role in protection against bacterial infection. We previously demonstrated that cathelicidin is induced by 1,25-dihydroxyvitamin D 3 (1,25(OH) 2 D 3 ) in human airway epithelial cells with a resultant increase in bactericidal activity. In this study we identify key factors that co-operate with 1,25(OH) 2 D 3 in the regulation of CAMP. Our results show for the first time that PU.1, the myeloid transcription factor (which has also been identified in lung epithelial cells), co-operates with the vitamin D receptor and CCAAT/enhancer binding protein α (CEBPα) to enhance the induction of CAMP in lung epithelial cells. Our findings also indicate that enhancement of 1,25(OH) 2 D 3 regulation of CAMP by histone deacetylase inhibitors involves co-operation between acetylation and chromatin remodeling through Brahma-related gene 1 (BRG1; a component of the SWItch/sucrose nonfermentable [SWI/SNF] complex). BRG1 can be an activator or repressor depending on BRG1-associated factors. Protein arginine methyltransferase 5 (PRMT5), a methlytransferase which interacts with BRG1, represses 1,25(OH) 2 D 3 induced CAMP in part through dimethylation of H4R3. Our findings identify key mediators involved in the regulation of the CAMP gene in lung epithelial cells and suggest new approaches for therapeutic manipulation of gene expression to increase the antibacterial capability of the airway.

KW - 1

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KW - cathelicidin

KW - histone acetylation

KW - protein arginine methyltransferase 5

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