CHD1 is a chromodomain-containing protein in the SNF2-like family of ATPases. Here we show that CHD1 exists predominantly as a monomer and functions as an ATP-utilizing chromatin assembly factor. This reaction involves purified CHD1, NAP1 chaperone, core histones and relaxed DNA. CHD1 catalyzes the ATP-dependent transfer of histones from the NAP1 chaperone to the DNA by a processive mechanism that yields regularly spaced nucleosomes. The comparative analysis of CHD1 and ACF revealed that CHD1 assembles chromatin with a shorter nucleosome repeat length than ACF. In addition, ACF, but not CHD1, can assemble chromatin containing histone H1, which is involved in the formation of higher-order chromatin structure and transcriptional repression. These results suggest a role for CHD1 in the assembly of active chromatin and a function of ACF in the assembly of repressive chromatin.

BackgroundFew studies have examined whether the healthcare needs of people living with rare diseases are being met. This study explores the experiences of Australian adults living with rare diseases in relation to diagnosis, information provision at the time of diagnosis, use of health and support services and involvement in research on their condition.MethodsThe survey respondents are self-selected from the population of Australian residents aged 18 years and over who are living with a rare disease. An online survey was implemented between July-August 2014. Purposive snowballing sampling was used. The results are reported as percentages with significant differences between sub-groups assessed using chi-squared analyses.ResultsEight hundred ten responses were obtained from adults living with a rare disease. 92.1 % had a confirmed diagnosis, of which 30.0 % waited five or more years for a diagnosis, 66.2 % had seen three or more doctors to get a diagnosis and 45.9 % had received at least one incorrect diagnosis. Almost three quarters (72.1 %) received no or not enough information at the time of diagnosis. In the 12 months prior to the survey, over 80 % of respondents had used the services of a general practitioner and a medical specialist while around a third had been inpatients at a hospital or had visited an emergency department. Only 15.4 % of respondents had ever used paediatric services, 52.8 % of these had experienced problems in the transition from paediatric to adult services. Only 20.3 % knew of a patient registry for their condition and 24.8 % were informed of clinical trials.ConclusionsThese findings suggest that not all healthcare needs of people living with rare diseases are being met. Structural changes to Australian healthcare systems may be required to improve the integration and coordination of diagnosis and care. Health professionals may need greater awareness of rare diseases to improve the diagnostic process and support to meet the information requirements of people newly diagnosed with rare diseases. Health service use is likely higher than for the general population and further epidemiological studies are needed on the impact of rare diseases on the healthcare system.

SUMMARY Chromatin assembly involves the combined action of histone chaperones and ATP-dependent motor proteins. Here we investigate the mechanism of nucleosome assembly with a purified chromatin assembly system containing the histone chaperone NAP1 and the ATP-dependent motor protein ACF. These studies revealed the rapid formation of a stable non-nucleosomal histone-DNA intermediate that is converted into canonical nucleosomes by ACF. The histone-DNA intermediate does not supercoil DNA like a canonical nucleosome, but has a nucleosome-like appearance by atomic force microscopy. This intermediate contains all four core histones, lacks NAP1, and is formed by the initial deposition of histones H3-H4. Conversion of the intermediate into histone H1-containing chromatin results in increased resistance to micrococcal nuclease digestion. These findings suggest that the histone-DNA intermediate corresponds to nascent nucleosome-like structures, such as those observed at DNA replication forks. Related complexes might be formed during other chromatin-directed processes such as transcription, DNA repair, and histone exchange.

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