Galectins are a family of secreted animal lectins with a high affinity to betagalactosides
commonly involved in cellular functions such as apoptosis, adhesion and
migration. Galectin 15 (LGALS15), a newest member of the galectin superfamily, has a
unique C-terminal RGD sequence and participates in integrin-mediated ovine
trophectoderm cell attachment and migration. In the ovine uterus, LGALS15 is
expressed only by the endometrial luminal (LE) and superficial glandular (sGE)
epithelia, induced by progesterone between Days 10 and 12 of the cycle and pregnancy,
and then stimulated by interferon tau (IFNT) from the conceptus after Day 14 of
pregnancy. During early pregnancy, the canonical janus kinase-signal transducer and
activator of transcription (JAK-STAT) pathway is not active in the endometrial LE/sGE.
Therefore, IFNT may utilizes a non-canonical signaling pathway to increase
transcription of genes, including CST3, CTSL, HIF2A, LGALS15, and WNT7A,
specifically in the endometrial LE/sGE. Alternatively, IFNT and progesterone could indirectly affect epithelial gene expression by influencing gene expression in the stroma,
which then communicates with the epithelium.
Although the LGALS15 gene is present in ovine, caprine and bovine species, it is
only expressed in uteri of sheep and goats. Available data shows a tissue- and speciesspecific
expression pattern for LGALS15, likely involving multiple layers of
transcription regulation in the ruminant endometrium. Further analysis of the LGALS15
5? promoter/enhancer region revealed similar predicted transcription factor binding sites
in all three species, including; PU.1, Ets-1, AP1, Sp1, and GRE or PRE sites.
Interestingly, the proximal promoter region of the LGALS15 gene in all three species
exhibited a conserved Sp1 binding site upstream of an AP1 binding site on both sense
and antisense strands, and with similar spacing between binding sites.
Sequence analysis revealed key differences in LGALS15 gene structure between
ruminant species including the proximity of repetitive DNA sequences to the
transcription start site (+1). Bovine LGALS15 has repetitive DNA sequences start at -
145 whereas in ovine or caprine LGALS15 it starts at about -300. The length of the
repetitive DNA sequence is similar (~1.2 kb) in the 5' promoter/enhancer region of
LGALS15 in all three species. Transient transfection analyses found that repetitive
DNA sequences reduced basal promoter activity and responsiveness to treatments. None
of the promoter construct showed responsiveness to interferon tau (IFNT). The bovine
LGALS15 gene promoter showed no activity under any experimental conditions. The
current studies indicate that uterine LGALS15 is expressed in ovine and caprine but not
bovine species. Additionally, repetitive DNA sequences found in the promoter region may contribute to modulating the LGALS15 gene expression. Therefore, the ruminant
LGALS15 gene, like other galectins, is under tight transcriptional control involving
hormones, requisite transcription factors and potentially chromatin remodeling
complexes working synergistically for LGALS15 promoter transactivation.
| Identifer | oai:union.ndltd.org:tamu.edu/oai:repository.tamu.edu:1969.1/ETD-TAMU-2009-08-7106 |
| Date | 2009 August 1900 |
| Creators | Lewis, Shaye K. |
| Contributors | Spencer, Thomas E., Bazer, Fuller W. |
| Source Sets | Texas A and M University |
| Language | en_US |
| Detected Language | English |
| Type | Book, Thesis, Electronic Dissertation, text |
| Format | application/pdf |
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