CCAAT/Enhancer-Binding Proteins Are Key Regulators of Human Type Two Deiodinase Expression in a Placenta Cell Line

Abstract

An appropriate concentration of intracellular T(3) is a critical determinant of placenta development and function and is mainly controlled by the activity of type II deiodinase (D2). The levels of this enzyme are finely regulated in different tissues by coordinated transcriptional mechanisms, which rely on dedicated promoter sequences (e.g. cAMP response element and TATA elements) that impart inducibility and tissue specificity to Dio2 mRNA expression. Here we show that CCAAT enhancer-binding proteins α and β (C/EBPα and C/EBPβ) promote Dio2 expression in the trophoblastic cell line JEG3 through a conserved CCAAT element, which is a novel key component of the Dio2 promoter code that confers tissue-specific expression of D2 in these cells. Increased C/EBPs levels potently induce Dio2 transcription, whereas their ablation results in loss of Dio2 mRNA. By measuring the activity of several deletion and point mutant promoter constructs, we have identified the functional CCAAT element responsible for this effect, which is located in close proximity to the most 5' TATA box. Notably, this newly identified sequence is highly conserved throughout the species and binds in vivo and in vitro C/EBP, indicating the relevance of this regulatory mechanism. Together, our results unveil a novel mechanism of regulation of D2 expression in a trophoblastic cell line, which may play a relevant role during placenta development.

Identification of loci associated with conception rate in primiparous Holstein cows

“…The sharing of TFBS at 26 loci suggests that there may be joint regulation of CCR1 and TBRD loci in fertility processes (see Additional file 2: Table S2 and Table S4). For example, C/EBPα has been linked to impaired fertility, likely through regulation of the lutenization and vascular cell development in C/EBPα/C/EBPβ knockout mice studies [53], and has been linked to placenta development in humans [54]. Similar to C/EBPα, the Nrf2:MafK heterodimer regulates placental development in rats [55].…”

Notch and NF-kB signaling pathways regulate miR-223/FBXW7 axis in T-cell acute lymphoblastic leukemia

“…Expression vectors used were: Flag-N3 IC , 30 HA-N3 IC , 8 N1 IC , 32 RBPjk and MAM, 33 p65 34 and C/EBPa. 35 Transient transfection of Jurkat cells, with siNotch3 (sc-37135; SCBT, Santa Cruz B., Santa Cruz, CA, USA) and its control (AM4611; Ambion), was carried out with Amaxa-Nucleofection (Lonza, Walkersville, MD, USA). Jurkat and Molt3 cells were transfected with 100 nM of Control (CN-001000-01-05; Thermo Scientific) or Mimic (C-300580-07-0005; Thermo Scientific) of hsa-miR-223 or Control (IN-001005-01-05; Thermo Scientific) or anti-miR (IH-300580-0005; Thermo Scientific) of hsa-miR-223, using NeonTransfection System (Invitrogen).…”

Rethinking the biological relationships of the thyroid hormones, l-thyroxine and 3,5,3′-triiodothyronine

“…ND = not detected. regulated by C/EBPα and C/EBPβ (Canettieri et al, 2012). In the case of R. catesbeiana, we noted similarity in TH-associated abundance profiles between dio2 and cebp1 (an ortholog of C/EBPα) mRNA in intestine.…”