» Articles » PMID: 18923650

Long-range Enhancer Associated with Chromatin Looping Allows AP-1 Regulation of the Peptidylarginine Deiminase 3 Gene in Differentiated Keratinocyte

Overview
Journal PLoS One
Date 2008 Oct 17
PMID 18923650
Citations 28
Authors
Affiliations
Soon will be listed here.
Abstract

Transcription control at a distance is a critical mechanism, particularly for contiguous genes. The peptidylarginine deiminases (PADs) catalyse the conversion of protein-bound arginine into citrulline (deimination), a critical reaction in the pathophysiology of multiple sclerosis, Alzheimer's disease and rheumatoid arthritis, and in the metabolism of the major epidermal barrier protein filaggrin, a strong predisposing factor for atopic dermatitis. PADs are encoded by 5 clustered PADI genes (1p35-6). Unclear are the mechanisms controlling the expression of the gene PADI3 encoding the PAD3 isoform, a strong candidate for the deimination of filaggrin in the terminally differentiating epidermal keratinocyte. We describe the first PAD Intergenic Enhancer (PIE), an evolutionary conserved non coding segment located 86-kb from the PADI3 promoter. PIE is a strong enhancer of the PADI3 promoter in Ca2+-differentiated epidermal keratinocytes, and requires bound AP-1 factors, namely c-Jun and c-Fos. As compared to proliferative keratinocytes, calcium stimulation specifically associates with increased local DNase I hypersensitivity around PIE, and increased physical proximity of PIE and PADI3 as assessed by Chromosome Conformation Capture. The specific AP-1 inhibitor nordihydroguaiaretic acid suppresses the calcium-induced increase of PADI3 mRNA levels in keratinocytes. Our findings pave the way to the exploration of deimination control during tumorigenesis and wound healing, two conditions for which AP-1 factors are critical, and disclose that long-range transcription control has a role in the regulation of the gene PADI3. Since invalidation of distant regulators causes a variety of human diseases, PIE results to be a plausible candidate in association studies on deimination-related disorders or atopic disease.

Citing Articles

Aryl hydrocarbon receptor and IL-13 signaling crosstalk in human keratinocytes and atopic dermatitis.

Proper S, Dwyer A, Appiagyei A, Felton J, Ben-Baruch Morgenstern N, Marlman J Front Allergy. 2024; 5:1323405.

PMID: 38344408 PMC: 10853333. DOI: 10.3389/falgy.2024.1323405.


Peptidyl Arginine Deiminases in Chronic Diseases: A Focus on Rheumatoid Arthritis and Interstitial Lung Disease.

Nava-Quiroz K, Lopez-Flores L, Perez-Rubio G, Rojas-Serrano J, Falfan-Valencia R Cells. 2023; 12(24).

PMID: 38132149 PMC: 10741699. DOI: 10.3390/cells12242829.


Deimination in epidermal barrier and hair formation.

Mechin M, Simon M Philos Trans R Soc Lond B Biol Sci. 2023; 378(1890):20220245.

PMID: 37778378 PMC: 10542453. DOI: 10.1098/rstb.2022.0245.


PAD4 and Its Inhibitors in Cancer Progression and Prognosis.

Zhu D, Lu Y, Wang Y, Wang Y Pharmaceutics. 2022; 14(11).

PMID: 36365233 PMC: 9699117. DOI: 10.3390/pharmaceutics14112414.


Prolonged FOS activity disrupts a global myogenic transcriptional program by altering 3D chromatin architecture in primary muscle progenitor cells.

Barutcu A, Elizalde G, Gonzalez A, Soni K, Rinn J, Wagers A Skelet Muscle. 2022; 12(1):20.

PMID: 35971133 PMC: 9377060. DOI: 10.1186/s13395-022-00303-x.


References
1.
Zhao J, Bilsland A, Hoare S, Keith W . Involvement of NF-Y and Sp1 binding sequences in basal transcription of the human telomerase RNA gene. FEBS Lett. 2003; 536(1-3):111-9. DOI: 10.1016/s0014-5793(03)00038-3. View

2.
Magan N, Szremska A, Isaacs R, Stowell K . Modulation of DNA topoisomerase II alpha promoter activity by members of the Sp (specificity protein) and NF-Y (nuclear factor Y) families of transcription factors. Biochem J. 2003; 374(Pt 3):723-9. PMC: 1223628. DOI: 10.1042/BJ20030032. View

3.
Shaulian E, Karin M . AP-1 as a regulator of cell life and death. Nat Cell Biol. 2002; 4(5):E131-6. DOI: 10.1038/ncb0502-e131. View

4.
Wang Y, Chang W . Induction of disease-associated keratin 16 gene expression by epidermal growth factor is regulated through cooperation of transcription factors Sp1 and c-Jun. J Biol Chem. 2003; 278(46):45848-57. DOI: 10.1074/jbc.M302630200. View

5.
Eferl R, Wagner E . AP-1: a double-edged sword in tumorigenesis. Nat Rev Cancer. 2003; 3(11):859-68. DOI: 10.1038/nrc1209. View