A locus control region generates distinct active placental lactogen and inactive growth hormone gene domains in term placenta that are disrupted with obesity
Bibliographic record
Abstract
INTRODUCTION: Placental villi include an outer syncytiotrophoblast (STB) layer and an inner layer of cytotrophoblasts (CTBs) that fuse to generate the STB layer in pregnancy. While activation of the locus containing the human (h) placental lactogen (hPL) genes (hPL-A/CSH1 and hPL-B/CSH2) begins in the CTBs, their expression in the STB requires epigenetic modifications and interactions between locus control region (LCR) and gene regulatory sequences. No factor that limits or facilitates hPL LCR/gene interactions for locus activation is reported. The paternally-expressed gene 3 (PEG3/PW1) transcription factor was pursued as a candidate. PEG3 is expressed by villous CTBs but not the STB and putative binding sites were identified in hPL-related sequences. METHODS: PEG3 expression was assessed in multiple cell types including in CTB-like JEG-3 cells. PEG3 binding was also assessed in JEG-3 cells and term placenta samples from women with or without maternal obesity, where chromosomal architecture of the hPL gene locus was also examined. RESULTS: In JEG-3 cells, PEG3 was found to bind to hypersensitive site (HS III-V) sequences within the LCR. Knockdown of PEG3 in these cells resulted in increased hPL gene expression. In term placenta, PEG3 binding at placenta-specific HS IV was increased with maternal obesity, where a decrease in hPL RNA levels is seen, while PEG3 binding was reduced in women with obesity who develop insulin-treated gestational diabetes mellitus (O/GDM + Ins), where increased hPL gene expression is observed. Chromatin conformation capture revealed distinct hPL gene domain interactions that are modified with maternal obesity but largely reversed in O/GDM + Ins, correlating with PEG3 binding. DISCUSSION: Decreased PEG3 binding may be required for hPL domain generation and expression during CTB to STB transition.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".