The transcription factor HAND2 up-regulates transcription of the IL15 gene in human endometrial stromal cells.
J Biol Chem
; 295(28): 9596-9605, 2020 07 10.
Article
en En
| MEDLINE
| ID: mdl-32444497
ABSTRACT
Cyclic changes of the human endometrium, such as proliferation, secretion, and decidualization, occur during regular menstrual cycles. Heart- and neural crest derivatives-expressed transcript 2 (HAND2) is a key transcription factor in progestin-induced decidualization of human endometrial stromal cells (ESCs). It has been suggested that HAND2 regulates interleukin 15 (IL15), a key immune factor required for the activation and survival of uterine natural killer (uNK) cells. Activated uNK cells can promote spiral artery remodeling and secrete cytokines to induce immunotolerance. To date, no studies have evaluated the transcription factors that regulate IL15 expression in human ESCs. In the present study, we examined whether HAND2 controls IL15 transcriptional regulation in human ESCs. Quantitative RT-PCR and histological analyses revealed that HAND2 and IL15 levels increase considerably in the secretory phase of human endometrium tissues. Results from ChIP-quantitative PCR suggested that HAND2 binds to a putative HAND2 motif, which we identified in the upstream region of the human IL15 gene through in silico analysis. Using a luciferase reporter assay, we found that the upstream region of the human IL15 gene up-regulates reporter gene activities in response to estradiol and a progestin representative (medroxyprogesterone) in ESCs. The upstream region of the human IL15 gene also exhibited increasing responsiveness to transfection with a HAND2 expression vector. Of note, deletion and substitution variants of the putative HAND2 motif in the upstream region of IL15 did not respond to HAND2 transfection. These findings confirm that HAND2 directly up-regulates human IL15 transcription in ESCs.
Palabras clave
FOXO; Forkhead box protein O1 (FOXO1); basic helix-loop-helix transcription factor (bHLH); decidualization; endometrium; gene expression; gene regulation; gene transcription; heart- and neural crest derivatives-expressed transcript 2 (HAND2); interleukin; interleukin 15 (IL15); reproduction; stromal cell
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Transcripción Genética
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Regulación hacia Arriba
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Interleucina-15
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Elementos de Respuesta
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Endometrio
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Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico
Tipo de estudio:
Prognostic_studies
Límite:
Adult
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Female
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Humans
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Middle aged
Idioma:
En
Revista:
J Biol Chem
Año:
2020
Tipo del documento:
Article