Histone variant H2BE enhances chromatin accessibility in neurons to promote synaptic gene expression and long-term memory.

Histone proteins affect gene expression through multiple mechanisms, including through exchange with histone variants. Recent findings link histone variants to neurological disorders, yet few are well studied in the brain. Most notably, widely expressed variants of H2B remain elusive. We applied recently developed antibodies, biochemical assays, and sequencing approaches to reveal broad expression of the H2B variant H2BE and defined its role in regulating chromatin structure, neuronal transcription, and mouse behavior. We find that H2BE is enriched at promoters, and a single unique amino acid allows it to dramatically enhance chromatin accessibility. Further, we show that H2BE is critical for synaptic gene expression and long-term memory. Together, these data reveal a mechanism linking histone variants to chromatin accessibility, transcriptional regulation, neuronal function, and memory. This work further identifies a widely expressed H2B variant and uncovers a single histone amino acid with profound effects on genomic structure.

Histone variant H2BE enhances chromatin accessibility in neurons to promote synaptic gene expression and long-term memory.

Regulation of histone proteins affects gene expression through multiple mechanisms including exchange with histone variants. However, widely expressed variants of H2B remain elusive. Recent findings link histone variants to neurological disorders, yet few are well studied in the brain. We applied new tools including novel antibodies, biochemical assays, and sequencing approaches to reveal broad expression of the H2B variant H2BE, and defined its role in regulating chromatin structure, neuronal transcription, and mouse behavior. We find that H2BE is enriched at promoters and a single unique amino acid allows it to dramatically enhance chromatin accessibility. Lastly, we show that H2BE is critical for synaptic gene expression and long-term memory. Together, these data reveal a novel mechanism linking histone variants to chromatin regulation, neuronal function, and memory. This work further identifies the first widely expressed H2B variant and uncovers a single histone amino acid with profound effects on genomic structure.

Attitudes on Equal Health Care Access versus Efficient Clinical Decisions across a Not-for-Profit Health Care System.

BACKGROUND: Professional roles within a hospital system may influence attitudes behind clinical decisions. OBJECTIVE: To determine participants' preferences about clinical decisions that either value equal health care access or efficiency. DESIGN: Deidentified survey asking participants to choose between offering a low-cost screening test to a whole population ("equal access") or a more sensitive, expensive test that could be given to only half of the population but resulting in 10% more avoided deaths ("efficient"). Data collection took place from August 18, 2021, to January 24, 2022. Study 1644 was determined to be exempt by Tufts Health Sciences Institutional Review Board (IRB). SETTING: Tufts Medicine Healthcare System. PARTICIPANTS: Approximately 15,000 hospital employees received an e-mail from the Tufts Medicine Senior Vice President of Academic Integration. MEASUREMENTS: Analysis of survey responses with chi-square and 1-sample t tests to determine the proportion who chose each option. Logistic regression models fit to examine relationships between professional role and test choice. RESULTS: A total of 1,346 participants completed the survey (∼9.0% response rate). Overall, approximately equal percentages of respondents chose the "equal access" (48%) and "efficient" option (52%). However, gender, professional role (categorical), and clinical role (dichotomous) were significantly associated with test choice. For example, among those in nonclinical roles, women were more likely than men to choose equal health care access. In multivariable analyses, having clinical roles was significantly associated with 1.73 times the likelihood of choosing equal access (95% confidence interval = 1.33-2.25). LIMITATIONS: Generalizability concerns and survey question wording limit the study results. CONCLUSION: Clinicians were more likely than nonclinicians to choose the equal health care access option, and health care administrators were more likely to choose efficiency. These differing attitudes can affect patient care and health care quality. HIGHLIGHTS: Divergent preferences of valuing equal health care access and efficiency may be in conflict during clinical decision making.In this cross-sectional study that included 1,346 participants, approximately equal percentages of respondents chose the "equal access" (48%) and "efficient" option (52%), a nonsignificant difference. However, gender, professional role (categorical), and clinical role (dichotomous) were significantly associated with test choiceSince clinicians were more likely than nonclinicians to choose the equal health care access option and health care administrators were more likely to choose efficiency, these differing attitudes can affect patient care and health care quality.