Rac1 GTPase and the Rac1 exchange factor Tiam1 associate with Wnt-responsive promoters to enhance beta-catenin/TCF-dependent transcription in colorectal cancer cells

<p>Abstract</p> <p>Background</p> <p>β-catenin is a key mediator of the canonical Wnt pathway as it associates with members of the T-cell factor (TCF) family at Wnt-responsive promoters to drive the transcription of Wnt target genes. Recently, we showed that Rac1 GTPase synergizes with β-catenin to increase the activity of a TCF-responsive reporter. This synergy was dependent on the nuclear presence of Rac1, since inhibition of its nuclear localization effectively abolished the stimulatory effect of Rac1 on TCF-responsive reporter activity. We hypothesised that Rac1 plays a direct role in enhancing the transcription of endogenous Wnt target genes by modulating the β-catenin/TCF transcription factor complex.</p> <p>Results</p> <p>We employed chromatin immunoprecipitation studies to demonstrate that Rac1 associates with the β-catenin/TCF complex at Wnt-responsive promoters of target genes. This association served to facilitate transcription, since overexpression of active Rac1 augmented Wnt target gene activation, whereas depletion of endogenous Rac1 by RNA interference abrogated this effect. In addition, the Rac1-specific exchange factor, Tiam1, potentiated the stimulatory effects of Rac1 on the canonical Wnt pathway. Tiam1 promoted the formation of a complex containing Rac1 and β-catenin. Furthermore, endogenous Tiam1 associated with endogenous β-catenin, and this interaction was enhanced in response to Wnt3a stimulation. Intriguingly, Tiam1 was recruited to Wnt-responsive promoters upon Wnt3a stimulation, whereas Rac1 was tethered to TCF binding elements in a Wnt-independent manner.</p> <p>Conclusion</p> <p>Taken together, our results suggest that Rac1 and the Rac1-specific activator Tiam1 are components of transcriptionally active β-catenin/TCF complexes at Wnt-responsive promoters, and the presence of Rac1 and Tiam1 within these complexes serves to enhance target gene transcription. Our results demonstrate a novel functional mechanism underlying the cross-talk between Rac1 and the canonical Wnt signalling pathway.</p

Growth and Nutritional Status of the Bharia – A Primitive Tribe of Madhya Pradesh

This study is an attempt to understand the physical growth and nutritional status of Bharia, a primitive tribe of Central India. A cross sectional study was conducted on 551 children (283 boys and 268 girls) aged 4 to 18 years. Body weight, height, sitting height, head circumference, upper arm circumference, chest circumference, biceps, triceps, sub scapular and calf skin fold thickness were measured. Body Mass Index was calculated as weight/ height2to calculate chronic energy deficiency. All anthropometric measurements except skin fold measurement exhibit uniform increase with age in both the sexes. Age-specific Body Mass Index (BMI) indicated substantial changes and falls during pre-school age and rise in adolescence. The BMI according to the Indian standard was normal, but when the data was compared with the International standard malnutrition in both sexes was noticed in childhood. Boys remained undernourished after adolescence, while girls reached the normal growth patterns

Growth and Nutritional Status of Pre-School Children in India: Rural-Urban and Gender Differences

This cross-sectional study of growth and nutritional status makes an attempt to find the gender and rural-urban differences among Indian preschool children. This study is based on the data of weight and height of children aged 0–35 months taken from 26 States (total 26,369 children; 13784 boys and 12585 girls). The children are found to be lighter and shorter compared to International standards irrespective of age and sex. Boys are heavier and taller than girls. Urban preschool children are heavier and taller compared to rural counterparts. In the urban area, higher percentages of girls are affected by underweight (37.1%) and stunting (35.0%) than boys. In rural areas, the prevalence of underweight is also higher among girls (47.9%) compared to boys (45.7%), which is found to be much significant (p< 0.01). There is a significant rural-urban as well as gender difference in growth and nutritional status of Indian preschool children

Influence of Ethnicity, Geography and Climate on the Variation of Stature among Indian Populations

This paper analyzes the variation in the mean stature of adult males of a variety of population groups in India and examines the influence of geographical, climatic and ethnic factors on it. A considerable variation in mean stature has been found with respect to these three attributes. Variation »between« ethnic groups compared with »within« ethnic groups was found to be much more than that of geographical and climatic zones. Scheduled Castes (SC) and Scheduled Tribes (ST) populations have much low average height than that of General Castes (GC). Climatically dry and semiarid zones have a tendency to have higher stature than in the Monsoon areas. The mean height has been found to be the highest in north India. It is closely followed by west India. An interesting feature is that as one goes towards east and south the mean height gradually decreases. It is the lowest in islands. The mean heights have been regressed on geographical, climatic and ethnic factors, after converting these factors into binary variables. The regression analysis has strengthened the findings, that there is a highly significant relationship between height and geographical, climatic and ethnic factors

Food practices in contrasting populations: an anthropological study of the Sherpas, Lepchas, Oraons and Mahishyas of West Bengal

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