Epigenetic modifications and chromatin loop organization explain the different expression profiles of the Tbrg4, WAP and Ramp3 genes.
Whey Acidic Protein (WAP) gene expression is specific to the mammary gland and regulated by lactogenic hormones to peak during lactation. It differs markedly from the more constitutive expression of the two flanking genes, Ramp3 and Tbrg4. Our results show that the tight regulation of WAP gene expression parallels variations in the chromatin structure and DNA methylation profile throughout the Ramp3-WAP-Tbrg4 locus. Three Matrix Attachment Regions (MAR) have been predicted in this locus. Two of them are located between regions exhibiting open and closed chromatin structures in the liver. The third, located around the transcription start site of the Tbrg4 gene, interacts with topoisomerase II in HC11 mouse mammary cells, and in these cells anchors the chromatin loop to the nuclear matrix. Furthermore, if lactogenic hormones are present in these cells, the chromatin loop surrounding the WAP gene is more tightly attached to the nuclear structure, as observed after a high salt treatment of the nuclei and the formation of nuclear halos. Taken together, our results point to a combination of several epigenetic events that may explain the differential expression pattern of the WAP locus in relation to tissue and developmental stages.
Montazer-Torbati
Mohammad Bagher
MB
UR1196, Unité de Génomique et Physiologie de la Lactation, INRA, Jouy en Josas, France.
Hue-Beauvais
Cathy
C
Droineau
Stéphanie
S
Ballester
Maria
M
Coant
Nicolas
N
Aujean
Etienne
E
Petitbarat
Marie
M
Rijnkels
Monique
M
Devinoy
Eve
E
D000818:Animals; D002460:Cell Line; D002843:Chromatin; D019175:DNA Methylation; D005786:Gene Expression Regulation / Q000502:physiology*; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008099:Liver; D008321:Mammary Glands, Animal; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D008894:Milk Proteins / Q000235:genetics*; D011817:Rabbits; D058264:Receptor Activity-Modifying Protein 3; D058261:Receptor Activity-Modifying Proteins
D002843:Chromatin; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D008894:Milk Proteins; C545507:Ramp3 protein, mouse; D058264:Receptor Activity-Modifying Protein 3; D058261:Receptor Activity-Modifying Proteins; C024471:whey acidic proteins