Villaescusa JC, et al reported the expression of Hox cofactor genes during mouse ovarian follicular development and oocyte maturation.
Very little is known about the expression and function of the HOX and HOX-cofactors genes in mammalian oogenesis. The aim of the present study was to determine the expression of PBX and PREP-1 gene products in the mouse ovary and their localization to particular ovarian compartment, specifically the oocyte-containing ovarian follicle. Immunocytochemical analysis demonstrated that PREP-1 was present in both granulosa cells and oocytes. PREP-1 was found in the nucleus in primary oocytes, but in the cytoplasm of fully-grown oocytes; in granulosa cells, however, PREP-1 was always localized to the nuclei. No PREP-1 immunoreactivity was found in corpus luteum, theca or stroma. PBX-1 was found in the cytosol of the oocyte, while PBX-2 expression was mostly restricted to the nuclei of granulosa cells. In addition, PBX-2 was also found in the nucleus of primary oocytes. Since PREP-PBX complexes act in vivo in conjunction with HOX transcription factors, we have used RT-PCR to identify HOX genes expressed in the ovary. This analysis identified transcripts for six HOX genes (A5, A9, B6, B7, C6 and C8) and two more TALE cofactors (PREP2 and Meis2). Thus, a number of HOX and HOX cofactor genes are expressed in the mammalian ovary. The restricted expression pattern for PBX-1 and PBX-2 and the changes in expression and localization of PREP-1 in the oocyte and granulosa cells suggest a previously unsuspected involvement of these transcription factors in oocyte maturation and development, as well as in granulosa cell differentiation.
NCBI Summary:
This gene encodes a ubiquitously expressed member of the TALE/PBX homeobox family. It was identified by its similarity to a homeobox gene which is involved in t(1;19) translocation in acute pre-B-cell leukemias. This protein is a transcriptional activator which binds to the TLX1 promoter. The gene is located within the major histocompatibility complex (MHC) on chromosome 6.
General function
Nucleic acid binding, DNA binding, Transcription factor
Comment
Cellular localization
Nuclear
Comment
Ovarian function
Comment
Expression regulated by
Comment
Ovarian localization
Oocyte, Granulosa
Comment
HOX cofactors expression and regulation in the human ovary. Ota T et al. ABSTRACT: BACKGROUND: HOX cofactors enhance HOX binding affinities and specificities and increase HOX's unique functional activities. The expression and the regulation of HOX cofactors in human ovaries are unknown. Methods: In this study, the expression of HOX cofactors, PBX1, PBX2, and MEIS1/2, were examined by using RT-PCR, immunofluorescence in cultured immortalized human granulosa (SVOG) cells. The distribution of these HOX cofactors in human ovaries was examined by immunohistochemistry. The effects of growth differentiation factor-9 (GDF-9) and follicle-stimulating hormone (FSH) on PBX2 in SVOG cells were investigated by western blot analysis. Binding activities of HOXA7 and PBX2 to the specific sequences in granulosa cells were determined by electrophoretic mobility shift assay (EMSA). Results and conclusions: In SVOG cells, PBX1, PBX2 and MEIS1/2 were expressed during cell culture. In normal human ovaries, PBX1 and MEIS1/2 were expressed in granulosa cells at essentially all stages of follicular development. These cofactors were expressed in the nuclei of the granulosa cells from the primordial to the secondary follicles, whereas beyond multilayered follicles was observed in the cytoplasm. The co-expression of PBX1 and MEIS1 in granulosa cells in normal human ovaries suggested that MEIS1 might control PBX1 sublocalization, as seen in other systems. PBX2 was not expressed or weakly expressed in the primordial follicles. From the primary follicles to the preovulatory follicles, PBX2 expression was inconsistent and the expression was found in the granulosa cell nuclei. The PBX2 expression pattern is similar to HOXA7 expression in ovarian follicular development. Furthermore, FSH down-regulated, GDF-9 did not change PBX2 expression, but co-treatment of the granulosa cells with FSH and GDF-9 up-regulated PBX2 expression. These results implicated a role for PBX2 expression in the steroidogenic activities of granulosa cells in humans. Moreover, PBX2 and HOXA7 bound together to the Pbx sequence, but not to the EMX2 promoter sequence, in SVOG cells. Our findings indicate that HOX cofactors expression in normal human ovary is temporally and spatially specific and regulated by FSH and GDF-9 in granulosa cells. HOX proteins may use different HOX cofactors, depending on DNA sequences that are specific to the granulosa cells.