optimized-analysis-dna-methylation-gene-expression-from-small

Optimized Analysis of DNA Methylation and Gene Expression from Small, Anatomically-defined Areas of the Brain

Exposure to diet, drugs and early life adversity during sensitive windows of life 1,2 can lead to lasting changes in gene expression that contribute to ...

Max Planck Institute of Psychiatry

ZAC1 (zinc finger protein regulating apoptosis and cell cycle arrest) is a member of the new subfamily of zinc-finger transcription factors, designated as PLAG (pleomorphic adenoma gene) family. The ZAC1 gene is maternally imprinted and is linked to developmental disorders such as growth retardation and transient neonatal diabetes mellitus. We wanted to assess whether the genetic variability of the ZAC1 gene was associated with anthropometric (weight, BMI, waist-to-hip ratio) or biochemical (plasma lipid, insulin, glucose levels, blood pressure level) phenotypes.

Study of the genetic variability of ZAC1 (PLAGL1) in French population-based samples.

Alternative splicing serves to increase biological diversity and adaptation. Many genes, including the glucocorticoid receptor (GR), contain multiple 5'-untranslated exons in their promoter regions that can give rise to various mRNA isoforms encoding the same protein. To date, information on the mouse GR promoter remains sparse. Here, we extensively characterize alternative first exons of the mouse GR to reveal homology to the rat and human. We further find that, although most promoters are broadly expressed in various tissues, transcription of individual promoters can be differentially regulated by growth factor- and depolarization-induced signaling. Moreover, in addition to selective promoter usage, the alternative first exon transcripts differentially control RNA stability and translation efficiency, indicative of their role in GR expression. In conclusion, the composite GR promoter enables multilayered adjustments in gene expression through transcriptional and posttranscriptional mechanisms that may serve varying physiological demands.

Differential regulation and function of 5'-untranslated GR-exon 1 transcripts.

&Eacute;pissage alternatif sert &agrave; augmenter la diversit&eacute; biologique et adaptation. Plusieurs g&egrave;nes, y compris le r&eacute;cepteur des glucocortico&iuml;des (GR), contiennent plusieurs exons non traduite de 5&#39; dans leurs r&eacute;gions promotrices qui peuvent donner lieu &agrave; diverses isoformes d&#39;ARNm codant pour la prot&eacute;ine m&ecirc;me. &Agrave; ce jour, les informations sur la souris promoteur GR reste clairsem&eacute;e. Ici, nous caract&eacute;risons intensivement les exons premi&egrave;res alternatives de la souris GR pour r&eacute;v&eacute;ler l&#39;homologie au rat et humaine. Plus loin, nous trouvons que, transcription de divers promoteurs peut &ecirc;tre r&eacute;glement&eacute;e par le facteur de croissance-d&eacute;polarisation induite et signalisation bien que la plupart des promoteurs sont largement exprim&eacute;es dans divers tissus, diff&eacute;remment. En outre, en plus de l&#39;utilisation du promoteur s&eacute;lectif, les transcriptions d&#39;exon premi&egrave;res alternative diff&eacute;rentiellement contr&ocirc;lent l&#39;efficacit&eacute; stabilit&eacute; et traduction RNA, indicative de leur r&ocirc;le dans l&#39;expression de GR. En conclusion, le promoteur GR composite permet des ajustements par multicouches dans l&#39;expression des g&egrave;nes par le biais de transcriptionnelles et post-transcriptionnelle des m&eacute;canismes qui peuvent servir &agrave; diverses exigences physiologiques.

R&eacute;gulation diff&eacute;rentielle et fonction de transcriptions de GR-exon 1 non traduite de 5&#39;.

Splicing alternativo serve per aumentare la diversit&agrave; biologica e adattamento. Molti geni, tra cui i recettori glucocorticoidi (GR), contengono pi&ugrave; esoni 5&#39;-non tradotta nelle loro regioni promotore che possono dare origine a diverse isoforme di mRNA codifica per la proteina stessa. Fino ad oggi, informazioni sul mouse promotore GR rimane scarsa. Qui, abbiamo ampiamente caratterizzano esoni alternativi primi del mouse GR per rivelare omologia di ratto e umani. Troviamo inoltre che, anche se la maggior parte dei promotori sono largamente espressi nei vari tessuti, trascrizione dei singoli promotori differenziale regolabile da fattore di crescita - e depolarizzazione indotta di segnalazione. Inoltre, oltre all&#39;utilizzo del promotore selettiva, le trascrizioni di esone alternativo prime controllano differenzialmente RNA traduzione di stabilit&agrave; e di efficienza, indicativo del loro ruolo nell&#39;espressione GR. In conclusione, il promotore GR composito consente multistrati regolazioni nell&#39;espressione genica attraverso meccanismi trascrizionali e posttranscriptional che possono servire diverse esigenze fisiologiche.

Article	Year
Molecular and cellular biology\| PubMed ID: 12529403	2003
The Journal of neuroscience : the official journal of the Society for Neuroscience\| PubMed ID: 15342744	2004
Analytical biochemistry\| PubMed ID: 16289443	2006
Psychiatry research\| PubMed ID: 16730377	2006
Molecular and cellular biology\| PubMed ID: 16809786	2006
Neuroscience and biobehavioral reviews\| PubMed ID: 16934871	2007
Cancer research\| PubMed ID: 17178896	2006
The European journal of neuroscience\| PubMed ID: 18001282	2007
Molecular and cellular biology\| PubMed ID: 18663001	2008
Study of the genetic variability of ZAC1 (PLAGL1) in French population-based samples. Journal of hypertension\| PubMed ID: 19155788	2009
Journal of clinical oncology : official journal of the American Society of Clinical Oncology\| PubMed ID: 19349541	2009
PloS one\| PubMed ID: 19357765	2009
Nature neuroscience\| PubMed ID: 19898468	2009
Molecular and cellular endocrinology\| PubMed ID: 20117169	2010
Genome biology\| PubMed ID: 20210983	2010
Epigenetics : official journal of the DNA Methylation Society\| PubMed ID: 20339319	2010
Aging\| PubMed ID: 20354272	2010
Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies\| PubMed ID: 21499172	2011
Differential regulation and function of 5'-untranslated GR-exon 1 transcripts. Molecular endocrinology (Baltimore, Md.)\| PubMed ID: 21527501	2011
Frontiers in psychiatry / Frontiers Research Foundation\| PubMed ID: 21647402	2011
Stress (Amsterdam, Netherlands)\| PubMed ID: 21854166	2011
BMC research notes\| PubMed ID: 21878091	2011
Methods in molecular biology (Clifton, N.J.)\| PubMed ID: 22113273	2012
Epigenomics\| PubMed ID: 22122084	2010
Current psychiatry reports\| PubMed ID: 22307409	2012
Molecular and cellular biology\| PubMed ID: 22547676	2012

Dietmar Spengler

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