RGD Reference Report - Abnormal epigenetic modifications in peripheral blood mononuclear cells from patients with alopecia areata. - Rat Genome Database

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Abnormal epigenetic modifications in peripheral blood mononuclear cells from patients with alopecia areata.

Authors: Zhao, M  Liang, G  Wu, X  Wang, S  Zhang, P  Su, Y  Yin, H  Tan, Y  Zhang, J  Lu, Q 
Citation: Zhao M, etal., Br J Dermatol. 2012 Feb;166(2):226-73. doi: 10.1111/j.1365-2133.2011.10646.x. Epub 2012 Jan 9.
RGD ID: 9587460
Pubmed: PMID:21936853   (View Abstract at PubMed)
DOI: DOI:10.1111/j.1365-2133.2011.10646.x   (Journal Full-text)

BACKGROUND: Alopecia areata (AA) is a hair loss disease caused by T-cell-mediated autoimmune reactions against anagen-stage hair follicles. Although the exact aetiology is poorly understood, there is evidence to suggest that both genetic and environmental factors are involved in AA pathogenesis. OBJECTIVES: To analyse DNA methylation and histone modification patterns in peripheral blood mononuclear cells (PBMCs) of patients with AA. METHODS: PBMC samples were obtained from 25 patients with AA and 20 healthy controls. Global DNA methylcytosine levels, as well as histone acetylation and methylation levels, were measured by enzyme-linked immunosorbent assay. mRNA expression levels were determined using real-time quantitative reverse transcription-polymerase chain reaction. RESULTS: Genomic DNA methylation in PBMCs of patients with AA was increased relative to controls. DNMT1, MBD1 and MBD4 expression levels were significantly higher in AA PBMCs than in controls, and DNMT1 transcription levels positively correlated with global DNA methylation levels in patient samples. Histone H3 acetylation was significantly increased and histone H3 lysine 4 methylation was significantly decreased in patient PBMCs compared with healthy controls. Histone H3 acetylation levels were positively correlated with AA disease severity, and with RANTES (CCL5) mRNA expression in PBMCs of patients with AA. These changes were accompanied by increased p300 (EP300), histone deacetylase 1 (HDAC1), myeloid/lymphoid or mixed lineage leukemia (MLL), SET7/9 (SETD7), G9A (EHMT2), JMJD2C (KDM4C) and JARID1A (KDM5A) expression, as well as reduced HDAC2, HDAC7, LSD1 (KDM1A), JMJD2A (KDM4A) and JMJD2B (KDM4B) expression. CONCLUSIONS: DNA methylation and histone modification status are altered in PBMCs of patients with AA, possibly due to the deregulation of epigenetic regulatory genes. These changes may contribute to the activation of pathological immune responses in AA.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
alopecia areata  IEP 9587460; 9587460; 9587460mRNA:increased expression:mononuclear cell:RGD 
alopecia areata  ISODNMT1 (Homo sapiens)9587460; 9587460mRNA:increased expression:mononuclear cell:RGD 
alopecia areata  ISOEHMT2 (Homo sapiens)9587460; 9587460mRNA:increased expression:mononuclear cell:RGD 
alopecia areata  IEP 9587460; 9587460mRNA:decreased expression:mononuclear cell:RGD 
alopecia areata  ISOHDAC1 (Homo sapiens)9587460; 9587460mRNA:increased expression:mononuclear cell:RGD 
alopecia areata  ISOHDAC2 (Homo sapiens)9587460; 9587460mRNA:decreased expression:mononuclear cell:RGD 
alopecia areata  ISOHDAC7 (Homo sapiens)9587460; 9587460mRNA:decreased expression:mononuclear cell:RGD 
alopecia areata  IEP 9587460; 9587460; 9587460mRNA:decreased expression:peripheral blood mononuclear cell (human)RGD 
alopecia areata  IEP 9587460; 9587460mRNA:increased expression:peripheral blood mononuclear cell (human)RGD 
alopecia areata  ISOKDM1A (Homo sapiens)9587460; 9587460mRNA:decreased expression:peripheral blood mononuclear cell (human)RGD 
alopecia areata  ISOKDM4A (Homo sapiens)9587460; 9587460mRNA:decreased expression:peripheral blood mononuclear cell (human)RGD 
alopecia areata  ISOKDM4B (Homo sapiens)9587460; 9587460mRNA:decreased expression:peripheral blood mononuclear cell (human)RGD 
alopecia areata  ISOKDM4C (Homo sapiens)9587460; 9587460mRNA:increased expression:peripheral blood mononuclear cell (human)RGD 
alopecia areata  ISOKDM5A (Homo sapiens)9587460; 9587460mRNA:increased expression:peripheral blood mononuclear cell (human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Dnmt1  (DNA methyltransferase 1)
Ehmt2  (euchromatic histone lysine methyltransferase 2)
Hdac1  (histone deacetylase 1)
Hdac2  (histone deacetylase 2)
Hdac7  (histone deacetylase 7)
Kdm1a  (lysine demethylase 1A)
Kdm4a  (lysine demethylase 4A)
Kdm4b  (lysine demethylase 4B)
Kdm4c  (lysine demethylase 4C)
Kdm5a  (lysine demethylase 5A)

Genes (Mus musculus)
Dnmt1  (DNA methyltransferase 1)
Ehmt2  (euchromatic histone lysine N-methyltransferase 2)
Hdac1  (histone deacetylase 1)
Hdac2  (histone deacetylase 2)
Hdac7  (histone deacetylase 7)
Kdm1a  (lysine (K)-specific demethylase 1A)
Kdm4a  (lysine (K)-specific demethylase 4A)
Kdm4b  (lysine (K)-specific demethylase 4B)
Kdm4c  (lysine (K)-specific demethylase 4C)
Kdm5a  (lysine demethylase 5A)

Genes (Homo sapiens)
DNMT1  (DNA methyltransferase 1)
EHMT2  (euchromatic histone lysine methyltransferase 2)
HDAC1  (histone deacetylase 1)
HDAC2  (histone deacetylase 2)
HDAC7  (histone deacetylase 7)
KDM1A  (lysine demethylase 1A)
KDM4A  (lysine demethylase 4A)
KDM4B  (lysine demethylase 4B)
KDM4C  (lysine demethylase 4C)
KDM5A  (lysine demethylase 5A)


Additional Information