Differential Localization and Independent Acquisition of the H3K9me2 and H3K9me3 Chromatin Modifications in the Caenorhabditis elegans Adult Germ Line

Histone methylation is a prominent feature of eukaryotic chromatin that modulates multiple aspects of chromosome function. Methyl modification can occur on several different amino acid residues and in distinct mono-, di-, and tri-methyl states. However, the interplay among these distinct modification states is not well understood. Here we investigate the relationships between dimethyl and trimethyl modifications on lysine 9 of histone H3 (H3K9me2 and H3K9me3) in the adult Caenorhabditis elegans germ line. Simultaneous immunofluorescence reveals very different temporal/spatial localization patterns for H3K9me2 and H3K9me3. While H3K9me2 is enriched on unpaired sex chromosomes and undergoes dynamic changes as germ cells progress through meiotic prophase, we demonstrate here that H3K9me3 is not enriched on unpaired sex chromosomes and localizes to all chromosomes in all germ cells in adult hermaphrodites and until the primary spermatocyte stage in males. Moreover, high-copy transgene arrays carrying somatic-cell specific promoters are highly enriched for H3K9me3 (but not H3K9me2) and correlate with DAPI-faint chromatin domains. We further demonstrate that the H3K9me2 and H3K9me3 marks are acquired independently. MET-2, a member of the SETDB histone methyltransferase (HMTase) family, is required for all detectable germline H3K9me2 but is dispensable for H3K9me3 in adult germ cells. Conversely, we show that the HMTase MES-2, an E(z) homolog responsible for H3K27 methylation in adult germ cells, is required for much of the germline H3K9me3 but is dispensable for H3K9me2. Phenotypic analysis of met-2 mutants indicates that MET-2 is nonessential for fertility but inhibits ectopic germ cell proliferation and contributes to the fidelity of chromosome inheritance. Our demonstration of the differential localization and independent acquisition of H3K9me2 and H3K9me3 implies that the trimethyl modification of H3K9 is not built upon the dimethyl modification in this context. Further, these and other data support a model in which these two modifications function independently in adult C. elegans germ cells

Dynamic Chromatin Organization during Foregut Development Mediated by the Organ Selector Gene PHA-4/FoxA

Central regulators of cell fate, or selector genes, establish the identity of cells by direct regulation of large cohorts of genes. In Caenorhabditis elegans, foregut (or pharynx) identity relies on the FoxA transcription factor PHA-4, which activates different sets of target genes at various times and in diverse cellular environments. An outstanding question is how PHA-4 distinguishes between target genes for appropriate transcriptional control. We have used the Nuclear Spot Assay and GFP reporters to examine PHA-4 interactions with target promoters in living embryos and with single cell resolution. While PHA-4 was found throughout the digestive tract, binding and activation of pharyngeally expressed promoters was restricted to a subset of pharyngeal cells and excluded from the intestine. An RNAi screen of candidate nuclear factors identified emerin (emr-1) as a negative regulator of PHA-4 binding within the pharynx, but emr-1 did not modulate PHA-4 binding in the intestine. Upon promoter association, PHA-4 induced large-scale chromatin de-compaction, which, we hypothesize, may facilitate promoter access and productive transcription. Our results reveal two tiers of PHA-4 regulation. PHA-4 binding is prohibited in intestinal cells, preventing target gene expression in that organ. PHA-4 binding within the pharynx is limited by the nuclear lamina component EMR-1/emerin. The data suggest that association of PHA-4 with its targets is a regulated step that contributes to promoter selectivity during organ formation. We speculate that global re-organization of chromatin architecture upon PHA-4 binding promotes competence of pharyngeal gene transcription and, by extension, foregut development

Work–Family Conflict and Job Outcomes Among Prison Officers in Ghana: A Test of Mediation and Moderation Processes

This study examines the mediating effect of job stress and the moderating effect of job autonomy on the relationship between work-to-family conflict (WFC) and job satisfaction and organizational commitment. It uses cross-sectional data from 1062 prison officers sampled from 31 prison establishments in Ghana. The results of structural equation modelling (SEM) analysis showed that WFC was negatively associated with job satisfaction and organizational commitment. Job stress significantly mediated the influence of WFC on job satisfaction and organizational commitment. The negative influence of WFC on job satisfaction and organizational commitment was less for prison officers with higher levels of job autonomy than for those with lower levels of autonomy. These findings suggest the need for correctional organizations to adopt family-friendly measures that facilitate officers’ ability to integrate their work and family responsibilities

Cognitive-behavioural interventions for preventing youth gang involvement for children and young people (7-16).

BACKGROUND: Many studies document a robust and consistent relationship between gang membership and elevated delinquency, with gang members disproportionately involved in crime compared to non-gang peers. Research also indicates that both delinquent youth and youth who join gangs often show a wide range of deficient or distorted social-cognitive processes compared to non-delinquent peers. Cognitive-behavioural interventions are designed to address cognitive deficits in order to reduce maladaptive or dysfunctional behaviour, and studies have documented their positive impact on a number of behavioural and psychological disorders among children and youth. OBJECTIVES: To determine the effectiveness of cognitive-behavioural interventions for preventing youth gang involvement for children and young people (ages 7-16). SEARCH STRATEGY: Electronic searches of ASSIA, CINAHL, CJA, Cochrane Library, Dissertations Abstracts A, EMBASE, ERIC, IBSS, LILACs, LexisNexis Butterworths, MEDLINE, NCJR Service Abstracts Database, PsycINFO, and Sociological Abstracts, to April 2007. Reviewers contacted relevant organisations, individuals, and list-servs and searched pertinent websites and reference lists. SELECTION CRITERIA: All randomised controlled trials or quasi-randomised controlled trials of interventions with a cognitive-behavioural intervention as the majority component, delivered to youth and children aged 7-16 not involved in a gang. DATA COLLECTION AND ANALYSIS: Searching yielded 2,284 unduplicated citations, 2,271 of which were excluded as irrelevant based on title and abstract. One was excluded following personal communication with investigators. One citation, of a large randomised prevention trial, awaits assessment; personal communication with study authors yielded unpublished reports addressing gang outcomes, but insufficient detail precluded determining inclusion status. Seven remaining reports were excluded as irrelevant because they were narrative reviews or descriptions of programs without evaluations, did not address a gang prevention programme, or did not address a gang prevention program that included a cognitive-behavioural intervention. The remaining four full-text reports excluded because of study design, leading to 0 included studies. MAIN RESULTS: No randomised controlled trials or quasi-randomised controlled trials were identified. AUTHORS' CONCLUSIONS: No evidence from randomised controlled trials or quasi-randomised controlled trials exists regarding the effectiveness of cognitive-behavioural interventions for gang prevention. Four evaluations of Gang Resistance Education and Training (GREAT) have been conducted, two of which were part of a US national evaluation, but all were excluded based on study design. Reviewers conclude there is an urgent need for rigorous primary evaluations of cognitive-behavioural interventions for gang prevention to develop this research field and guide future gang prevention programmes and policies