DNA methylation dynamics during intestinal stem cell differentiation reveals enhancers driving gene expression in the villus

Background: DNA methylation is of pivotal importance during development. Previous genome-wide studies identified numerous differentially methylated regions upon differentiation of stem cells, many of them associated with transcriptional start sites. Results: We present the first genome-wide, single-base-resolution view into DNA methylation dynamics during differentiation of a mammalian epithelial stem cell: the mouse small intestinal Lgr5+ stem cell. Very little change was observed at transcriptional start sites and our data suggest that differentiation-related genes are already primed for expression in the stem cell. Genome-wide, only 50 differentially methylated regions were identified. Almost all of these loci represent enhancers driving gene expression in the differentiated part of the small intestine. Finally, we show that binding of the transcription factor Tcf4 correlates with hypo-methylation and demonstrate that Tcf4 is one of the factors contributing to formation of differentially methylated regions. Conclusions: Our results reveal limited DNA methylation dynamics during small intestine stem cell differentiation and an impact of transcription factor binding on shaping the DNA methylation landscape during differentiation of stem cells in vivo

An Evaluation of the parents plus programme for pre-school children with conduct problems: A comparison of those with and without developmental disabilities

TThis study examined the effectiveness of the Parents Plus Programme for families of pre-school children with significant behavioural problems, comparing those with and without developmental disabilities. Twenty-two parents of children with developmental disabilities and conduct problems (the disability group), and 17 parents of children with conduct problems, but without developmental disabilities (the conduct problems group), were assessed before and after participating in the Parents Plus Programme, and at 10 months follow-up. More than 70% of cases in both the disability and conduct problems groups showed clinically significant improvement on the Total Difficulties scale of the Strengths and Difficulties Questionnaire. During the follow-up period, parents in the disability group showed a deterioration in psychological adjustment (on the General Health Questionnaire-12), while parents in the conduct problems group showed an improvement. Parents in the disability group reported a higher level of goal attainment compared with parents in the conduct problem group. Parents in both the disability and conduct problems groups evaluated the Parents Plus Programme equally positively. The Parents Plus Programme requires refinement to become more effective for families of pre-school children with developmental disabilities.Author has checked copyrightAD 20/01/201