LRH-1 drives colon cancer cell growth by repressing the expression of the <i>CDKN1A</i> gene in a p53-dependent manner

Liver receptor homologue 1 (LRH-1) is an orphan nuclear receptor that has been implicated in the progression of breast, pancreatic and colorectal cancer (CRC). To determine mechanisms underlying growth promotion by LRH-1 in CRC, we undertook global expression profiling following siRNA-mediated LRH-1 knockdown in HCT116 cells, which require LRH-1 for growth and in HT29 cells, in which LRH-1 does not regulate growth. Interestingly, expression of the cell cycle inhibitor p21 (CDKN1A) was regulated by LRH-1 in HCT116 cells. p21 regulation was not observed in HT29 cells, where p53 is mutated. p53 dependence for the regulation of p21 by LRH-1 was confirmed by p53 knockdown with siRNA, while LRH-1-regulation of p21 was not evident in HCT116 cells where p53 had been deleted. We demonstrate that LRH-1-mediated p21 regulation in HCT116 cells does not involve altered p53 protein or phosphorylation, and we show that LRH-1 inhibits p53 recruitment to the p21 promoter, likely through a mechanism involving chromatin remodelling. Our study suggests an important role for LRH-1 in the growth of CRC cells that retain wild-type p53

Meiosis genes in Daphnia pulex and the role of parthenogenesis in genome evolution

<p>Abstract</p> <p>Background</p> <p>Thousands of parthenogenetic animal species have been described and cytogenetic manifestations of this reproductive mode are well known. However, little is understood about the molecular determinants of parthenogenesis. The <it>Daphnia pulex </it>genome must contain the molecular machinery for different reproductive modes: sexual (both male and female meiosis) and parthenogenetic (which is either cyclical or obligate). This feature makes <it>D. pulex </it>an ideal model to investigate the genetic basis of parthenogenesis and its consequences for gene and genome evolution. Here we describe the inventory of meiotic genes and their expression patterns during meiotic and parthenogenetic reproduction to help address whether parthenogenesis uses existing meiotic and mitotic machinery, or whether novel processes may be involved.</p> <p>Results</p> <p>We report an inventory of 130 homologs representing over 40 genes encoding proteins with diverse roles in meiotic processes in the genome of <it>D. pulex</it>. Many genes involved in cell cycle regulation and sister chromatid cohesion are characterized by expansions in copy number. In contrast, most genes involved in DNA replication and homologous recombination are present as single copies. Notably, <it>RECQ2 </it>(which suppresses homologous recombination) is present in multiple copies while <it>DMC1 </it>is the only gene in our inventory that is absent in the <it>Daphnia </it>genome. Expression patterns for 44 gene copies were similar during meiosis <it>versus </it>parthenogenesis, although several genes displayed marked differences in expression level in germline and somatic tissues.</p> <p>Conclusion</p> <p>We propose that expansions in meiotic gene families in <it>D. pulex </it>may be associated with parthenogenesis. Taking into account our findings, we provide a mechanistic model of parthenogenesis, highlighting steps that must differ from meiosis including sister chromatid cohesion and kinetochore attachment.</p

SPATA18, a Spermatogenesis-Associated Gene, Is a Novel Transcriptional Target of p53 and p63▿

The transcription factor p53 functions not only to suppress tumorigenesis but also to maintain normal development and homeostasis. Although p53 was implicated in different aspects of fertility, including spermatogenesis and implantation, the mechanism underlying p53 involvement in spermatogenesis is poorly resolved. In this study we describe the identification of a spermatogenesis-associated gene, SPATA18, as a novel p53 transcriptional target and show that SPATA18 transcription is induced by p53 in a variety of cell types of both human and mouse origin. p53 binds a consensus DNA motif that resides within the first intron of SPATA18. We describe the spatiotemporal expression patterns of SPATA18 in mouse seminiferous tubules and suggest that SPATA18 transcription is regulated in vivo by p53. We also demonstrate the induction of SPATA18 by p63 and suggest that p63 can compensate for the loss of p53 activity in vivo. Our data not only enrich the known collection of p53 targets but may also provide insights on spermatogenesis defects that are associated with p53 deficiency

Floral diversity during Plio-Pleistocene Siwalik sedimentation (Kimin Formation) in Arunachal Pradesh, India, and its palaeoclimatic significance

A morpho-taxonomic study of leaf remains from the upper part of the Siwalik succession of sediments (Kimin Formation; upper Pliocene to lower Pleistocene) of Papumpare district, Arunachal Pradesh, India, revealed 23 species representing 20 genera belonging to 15 angiosperm families. The recovered fossil leaves are comparable to modern Bambusa tulda Roxb. (Poaceae), Mangifera indica Linn., Dracontomelum mangiferum Blume (Anacardiaceae); Chonemorpha macrophylla G. Don (Apocynaceae); Pongamia pinnata (L) Pierre., Millettia pachycarpa Benth., Dalbergia rimosa Roxb., Millettia extensa (Fabaceae); Macaranga denticulate Muell. Arg., Croton caudatus Geisel. (Euphorbiaceae); Combretum decandrum Roxb. (Combretaceae); Dysoxylum procerum Hiern. (Meliaceae); Dipterocarpus sp. Gaertn.f. (Dipterocarpaceae); Actinodaphne angustifolia Nees., Actinodaphne obovata Blume., Lindera pulcherrima Benth., Litsea salicifolia Roxb. (Lauraceae); Calophyllum polyanthum Wall. (Clusiaceae); Knema glaucescens Hook.f. (Myristaceae); Canarium bengalense Roxb. (Burseraceae); Quercus lamellose Smith; Quercus semicarpifolia Smith (Fagaceae); and Berchemia floribunda Wall. (Rhamnaceae). Among these taxa, 11 species are recorded as new to the Neogene flora of India. Analysis of the floral assemblage with respect to the distribution pattern of modern equivalent taxa and the physiognomic characters of the fossil leaves, suggests that a tropical evergreen forest was growing in a warm humid climate in the region at the time of deposition. This is in contrast to modern tropical semi-evergreen forests that occupy the area. Values of mean annual temperature (MAT) of 29.3°C and mean annual precipitation (MAP) of 290 mm have been calculated using leaf-margin characters and fossil leaf size