Transcriptomics

Dataset Information

4

ZNF750 in late keratinocyte differentiation


ABSTRACT: Disrupted skin barrier due to altered keratinocyte differentiation is common in pathologic conditions such as atopic dermatitis, ichthyosis and psoriasis. However, the molecular cascades governing keratinocyte terminal differentiation are still poorly understood. We have previously demostrated that a dominante mutation in ZNF750 leads to a clinical phenotype that reminiscent of psoriasis and seborrehic dermatitis. We defined ZNF750 as a nuclear effector that is atrongly activated in and essiential for keratinocyte terminal differentiation. ZNF750 knockdown in HaCaT keratinocytes markedly reduced the expression of epidermal late differentiation markers, including gene subsets of epidermal differentiation complex and skin barrier formation such as FLG, LOR, SPINK5, ALOX12B and DSG1, known to be mutated in various human skin diseases. Furthermore, ZNF750 over-expression in undifferentiated cells induced terminal differentiation genes. Thus, ZNF750 is a regulator of keratinocyte terminal differnetiation, and with its downstream targets can serve in future elucidation of therapeutics for common disease of skin barrier Gene expression analysis: To determine the differentaition signature for HaCaT keratinocytes, with ZNF750 gene silencing, total RNA was isolated in biologic triplicates from cells induced to differentiate for twelve days and hybridized to Affymerix Human Gene 1.0 ST arrays.

ORGANISM(S): Homo sapiens  

SUBMITTER: Idan Cohen   O S Birk  I Cohen  R Y Birnbaum 

PROVIDER: E-GEOD-38039 | ArrayExpress | 2012-09-24

SECONDARY ACCESSION(S): GSE38039PRJNA167082

REPOSITORIES: GEO, ArrayExpress

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Publications

ZNF750 is expressed in differentiated keratinocytes and regulates epidermal late differentiation genes.

Cohen Idan I   Birnbaum Ramon Y RY   Leibson Keren K   Taube Ran R   Sivan Sara S   Birk Ohad S OS  

PloS one 20120824 8


Disrupted skin barrier due to altered keratinocyte differentiation is common in pathologic conditions such as atopic dermatitis, ichthyosis and psoriasis. However, the molecular cascades governing keratinocyte terminal differentiation are poorly understood. We have previously demonstrated that a dominant mutation in ZNF750 leads to a clinical phenotype reminiscent of psoriasis and seborrheic dermatitis. Here we show that ZNF750 is a nuclear protein bearing a functional C-terminal nuclear localiz  ...[more]

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