instruction:
In this task, you are given an abstract of article. Your task is to generate title for this article. Preferred titles are under thirty words.
question:
Transcription factors (TFs) bind specifically to discrete regions of mammalian genomes called cis-regulatory elements. Among those are enhancers, which play key roles in regulation of gene expression during development and differentiation. Despite the recognized central regulatory role exerted by chromatin in control of TF functions, much remains to be learned regarding the chromatin structure of enhancers and how it is established. Here, we have analyzed on a genomic-scale enhancers that recruit FOXA1, a pioneer transcription factor that triggers transcriptional competency of these cis-regulatory sites. Importantly, we found that FOXA1 binds to genomic regions showing local DNA hypomethylation and that its cell-type-specific recruitment to chromatin is linked to differential DNA methylation levels of its binding sites. Using neural differentiation as a model, we showed that induction of FOXA1 expression and its subsequent recruitment to enhancers is associated with DNA demethylation. Concomitantly, histone H3 lysine 4 methylation is induced at these enhancers. These epigenetic changes may both stabilize FOXA1 binding and allow for subsequent recruitment of transcriptional regulatory effectors. Interestingly, when cloned into reporter constructs, FOXA1-dependent enhancers were able to recapitulate their cell type specificity. However, their activities were inhibited by DNA methylation. Hence, these enhancers are intrinsic cell-type-specific regulatory regions of which activities have to be potentiated by FOXA1 through induction of an epigenetic switch that includes notably DNA demethylation.
answer:
Epigenetic switch involved in activation of pioneer factor FOXA1-dependent enhancers.

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Background Spinocerebellar ataxia type 1 (SCA1) is a dominantly inherited neurodegenerative disorder characterized by progressive motor and cognitive dysfunction. Caused by an expanded polyglutamine tract in ataxin 1 (ATXN1), SCA1 pathogenesis involves a multifactorial process that likely begins with misfolding of ATXN1, which has functional consequences on its interactions, leading to transcriptional dysregulation. Because lithium has been shown to exert neuroprotective effects in a variety of conditions, possibly by affecting gene expression, we tested the efficacy of lithium treatment in a knock-in mouse model of SCA1 (Sca1154Q/2Q mice) that replicates many features of the human disease. Methods and Findings Sca1154Q/2Q mice and their wild-type littermates were fed either regular chow or chow that contained 0.2% lithium carbonate. Dietary lithium carbonate supplementation resulted in improvement of motor coordination, learning, and memory in Sca1154Q/2Q mice. Importantly, motor improvement was seen when treatment was initiated both presymptomatically and after symptom onset. Neuropathologically, lithium treatment attenuated the reduction of dendritic branching in mutant hippocampal pyramidal neurons. We also report that lithium treatment restored the levels of isoprenylcysteine carboxyl methyltransferase (Icmt; alternatively, Pccmt), down-regulation of which is an early marker of mutant ATXN1 toxicity. Conclusions The effect of lithium on a marker altered early in the course of SCA1 pathogenesis, coupled with its positive effect on multiple behavioral measures and hippocampal neuropathology in an authentic disease model, make it an excellent candidate treatment for human SCA1 patients.
answer:
Lithium Therapy Improves Neurological Function and Hippocampal Dendritic Arborization in a Spinocerebellar Ataxia Type 1 Mouse Model

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CONTEXT Trabecular bone score (TBS) is a novel texture index that evaluates the pixel gray-level variations in lumbar spine dual-energy X-ray absorptiometry images and is related to bone microarchitecture independent of bone mineral density (BMD).
OBJECTIVE We investigated lumbar spine TBS as an indicator for skeletal deterioration in diabetes.
DESIGN AND SETTING Cross-sectional data were collected from subjects participating in an ongoing prospective, community-based, cohort study from 2009 to 2010.
PARTICIPANTS We included 1229 men and 1529 postmenopausal women older than 50 years in the Ansung cohort.
OUTCOME MEASURES Biochemical parameters, lumbar spine TBS, and BMD from dual-energy X-ray absorptiometry images were measured.
RESULTS Lumbar spine TBS was lower in men with diabetes than in nondiabetic men (1.287 0.005 vs 1.316 0.003, P < .001), whereas lumbar spine BMD was higher in men with diabetes (1.135 0.010 vs 1.088 0.006 g/cm(2)). Lumbar spine TBS was lower in women with diabetes than in nondiabetic women only in an unadjusted model (1.333 0.004 vs 1.353 0.003). However, women younger than 65 years (n = 707) with diabetes had a lower TBS than those without diabetes, even after adjusted for covariates (P < .001). Diabetes was not associated with BMD at femur sites in both genders. TBS was negatively correlated with glycated hemoglobin, fasting plasma glucose, fasting insulin, and homeostasis model assessment for insulin resistance but not with homeostasis model assessment for -cell function in both genders.
CONCLUSIONS The inverse association between lumbar spine TBS and insulin resistance may make it an indicator for determining skeletal deterioration in diabetic patients who have high BMD.
answer:
Trabecular bone score as an indicator for skeletal deterioration in diabetes.