Evidence map›Paper›PMID 17636034›Full record

ArticleMolecular and cellular biology2007

Epigenetic activation of the human growth hormone gene cluster during placental cytotrophoblast differentiation.

Atsushi P Kimura, Daria Sizova, Stuart Handwerger, Nancy E Cooke, Stephen A Liebhaber

Open access · greenAbstract read
In one paragraph

Article in Molecular and cellular biology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
2.4field-weighted citation impact, top 12% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

18 citing papers in PubMed, 48 citations in OpenAlex.

  1. Article
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  8. Bridging sequence diversity and tissue-specific expression by DNA methylation in genes of the mouse prolactin superfamily.Mammalian genome : official journal of the International Mammalian Genome Society · 2012
    Article
  9. Article
  10. Review
  11. Lactogens and estrogens in breast cancer chemoresistance.Expert review of endocrinology & metabolism · 2011
    Article
  12. Article
  13. Review
  14. Article
  15. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 2 institutions in 1 country.

Atsushi P KimuraDepartment of Genetics, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Daria Sizova
Stuart Handwerger
Nancy E Cooke
Stephen A Liebhaber
University of Pennsylvania · USUniversity of Cincinnati · US

Funding

UNIVERSITY OF PENNSYLVANIA CAN CTR SUPPORT GRANTP30CA016520 · NCI · UNIVERSITY OF PENNSYLVANIA · PI SHELLEY L BERGER · 1985 to 2026
$222.3M
VIRAL VECTOR COREP30DK019525 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI MITCHELL A. LAZAR · 1986 to 2026
$48.3M
TRANSGENIC AND CHIMERIC MOUSE COREP30DK050306 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI Ken Hashigiwa Cadwell · 1997 to 2026
$32.5M
SOMATOGENIC/LACTOGENIC HORMONES OF PLACENTA/PITUITARYR01HD025147 · NICHD · UNIVERSITY OF PENNSYLVANIA · PI LIEBHABER, STEPHEN AARON · 1989 to 2014
$5.4M
Activation of Human Placental Hormonal ExpressionR01HD046737 · NICHD · UNIVERSITY OF PENNSYLVANIA · PI LIEBHABER, STEPHEN AARON · 2004 to 2013
$4.1M
MAYO REHABILITATION RESEARCH TRAINING PROGRAMT32HD007447 · NICHD · MAYO CLINIC ROCHESTER · PI BASFORD, JEFFREY R. · 1993 to 2012
$3.1M
THE PHYSIOLOGY OF PLACENTAL LACTOGENR01HD007447 · NICHD · DUKE UNIVERSITY · PI HANDWERGER, STUART · 1985 to 2006
$1.9M
The Physiology of Placental LactogenR56HD007447 · NICHD · CINCINNATI CHILDRENS HOSP MED CTR · PI HANDWERGER, STUART · 2008 to 2008
$319k
NCI NIH HHS P30 CA016520NICHD NIH HHS HD07447NICHD NIH HHS HD25147NICHD NIH HHS HD46737NICHD NIH HHS R01 HD007447NICHD NIH HHS R01 HD025147NICHD NIH HHS R01 HD046737NICHD NIH HHS R56 HD007447NICHD NIH HHS T32 HD007447NIDDK NIH HHS P30 DK019525NIDDK NIH HHS P30 DK050306
6 · The paper itself

Abstract

The hGH cluster contains a single human pituitary growth hormone gene (hGH-N) and four placenta-specific paralogs. Activation of the cluster in both tissues depends on 5' remote regulatory elements. The pituitary-specific locus control elements DNase I-hypersensitive site I (HSI) and HSII, located 14.5 kb 5' of the cluster (position -14.5), establish a continuous domain of histone acetylation that extends to and activates hGH-N in the pituitary gland. In contrast, histone modifications in placental chromatin are restricted to the more 5'-remote HSV-HSIII region (kb -28 to -32) and to the placentally expressed genes in the cluster, with minimal modification between these two regions. These data predict distinct modes of hGH cluster gene activation in the pituitary and placenta. Here we used cell culture models to track structural changes at the hGH locus through placental-gene activation. The data revealed that this process was initiated in primary cytotrophoblasts by histone H3K4 di- and trimethylation and H4 acetylation restricted to HSV and to the individual placental-gene repeat (PGR) units within the cluster. Later stages of transcriptional induction were accompanied by enhancement and extension of these modifications and by robust H3 acetylation at HSV, at HSIII, and throughout the placental-gene regions. These data suggested that elements restricted to HSIII-HSV regions and each individual PGR might be sufficient for activation of the hCS genes. This model was tested by comparing hCS transgene expression in the placentas of mouse embryos carrying a full hGH cluster to that in placentas in which the HSIII-HSV region was directly linked to the individual hCS-A PGR unit. The findings indicate that the HSIII-HSV region and the PGR units, although targeted for initial chromatin structural modifications, are insufficient to activate gene expression and that this process is dependent on additional, as-yet-unidentified chromatin determinants.

Indexed as

Cell DifferentiationEpigenesis, GeneticCells, CulturedChromatin ImmunoprecipitationFemaleHuman Growth HormoneHumansModels, GeneticMultigene FamilyPlacentaPregnancyPregnancy Trimester, ThirdTrophoblastsHuman Growth Hormone

Identifiers

PMID17636034
PMCPMC2099626
OpenAlexW2139394656

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.