Survey of the 2020 Fellowship Council application and match process and the impact of COVID-19.

BACKGROUND: The interview process represents a necessary but potentially resource intensive process from applicant and program perspectives. This study aimed to identify opinions of the 2020 Fellowship Council (FC) application and match process and in-cycle transition to virtual interviews due to the COVID-19 pandemic. METHODS: Surveys were developed to assess the interview process and were distributed by the FC to all applicants and fellowship programs. Completion was voluntary and data (median [IQR] reported) were anonymous. RESULTS: Applicant response was 53%. Applicants submitted 27.5 (13.25-40) applications, were offered 10 (4-17) interviews, and ranked 10 (5-15) programs. Due to COVID-19, 74% of interview plans changed. Applicants completed 30% of their planned in-person interviews. For decision-making, 90% felt that in-person and 81% virtual interviews were sufficiently informative. Expected cost was $4750 ($2000-$6000) vs. actual cost $1000 ($250-$2250), (p < 0.05). Expected missed work-days were 10 (5-16) versus actual 3 (0-6.25) (p < 0.05). For future interviews, 44% of applicants preferred in-person after virtual pre-interviews, 29% preferred virtual only, and 18% preferred in-person only. Program response was 38%. Programs received 60 (43-85.5) applications, offered 20 (15-26) interviews, completed 16 (12.5-21) interviews, and ranked 14 (10-18) candidates. For decision-making, 92% of programs felt in-person versus 71% virtual interviews were sufficiently informative. Person-hours were greater for in-person 48 (27.5-80) versus virtual 24 (9-40) interviews (p < 0.05). For future interviews, 38% of programs preferred in-person after virtual pre-interviews, 31% preferred in-person only, and 21% preferred virtual only. CONCLUSION: Despite pandemic changes, 81% of applicants and 71% of programs felt they gained sufficient information from virtual sessions to create rank lists. Virtual interviews had lower costs and fewer missed work-days for applicants and decreased resource usage for programs. The majority of both groups preferred either solely virtual or virtual pre-interview followed by in-person interview formats. Virtual interviews should be incorporated into future fellowship application cycles.

E2f6-mediated repression of the meiotic Stag3 and Smc1ß genes during early embryonic development requires Ezh2 and not the de novo methyltransferase Dnmt3b.

The E2f6 transcriptional repressor is an E2F-family member essential for the silencing of a group of meiosis-specific genes in somatic tissues. Although E2f6 has been shown to associate with both polycomb repressive complexes (PRC) and the methyltransferase Dnmt3b, the cross-talk between these repressive machineries during E2f6-mediated gene silencing has not been clearly demonstrated yet. In particular, it remains largely undetermined when and how E2f6 establishes repression of meiotic genes during embryonic development. We demonstrate here that the inactivation of a group of E2f6 targeted genes, including Stag3 and Smc1ß, first occurs at the transition from mouse embryonic stem cells (ESCs) to epiblast stem cells (EpiSCs), which represent pre- and post-implantation stages, respectively. This process was accompanied by de novo methylation of their promoters. Of interest, despite a clear difference in DNA methylation status, E2f6 was similarly bound to the proximal promoter regions both in ESCs and EpiSCs. Neither E2f6 nor Dnmt3b overexpression in ESCs decreased meiotic gene expression or increased DNA methylation, indicating that additional factors are required for E2f6-mediated repression during the transition. When the SET domain of Ezh2, a core subunit of the PRC2 complex, was deleted, however, repression of Stag3 and Smc1ß during embryoid body differentiation was largely impaired, indicating that the event required the enzymatic activity of Ezh2. In addition, repression of Stag3 and Smc1ß occurred in the absence of Dnmt3b. The data presented here suggest a primary role of PRC2 in E2f6-mediated gene silencing of the meiotic genes.