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Selective binding of retrotransposons by ZFP352 facilitates the timely dissolution of totipotency network.

ABSTRACT: Acquisition of new stem cell fates relies on the dissolution of the prior regulatory network sustaining the existing cell fates. Currently, extensive insights have been revealed for the totipotency regulatory network around the zygotic genome activation (ZGA) period. However, how the dissolution of the totipotency network is triggered to ensure the timely embryonic development following ZGA is largely unknown. In this study, we identify the unexpected role of a highly expressed 2-cell (2C) embryo specific transcription factor, ZFP352, in facilitating the dissolution of the totipotency network. We find that ZFP352 has selective binding towards two different retrotransposon sub-families. ZFP352 coordinates with DUX to bind the 2C specific MT2_Mm sub-family. On the other hand, without DUX, ZFP352 switches affinity to bind extensively onto SINE_B1/Alu sub-family. This leads to the activation of later developmental programs like ubiquitination pathways, to facilitate the dissolution of the 2C state. Correspondingly, depleting ZFP352 in mouse embryos delays the 2C to morula transition process. Thus, through a shift of binding from MT2_Mm to SINE_B1/Alu, ZFP352 can trigger spontaneous dissolution of the totipotency network. Our study highlights the importance of different retrotransposons sub-families in facilitating the timely and programmed cell fates transition during early embryogenesis.

SUBMITTER: Li Z

PROVIDER: S-EPMC10281998 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature

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Selective binding of retrotransposons by ZFP352 facilitates the timely dissolution of totipotency network.

Li Zhengyi Z Xu Haiyan H Li Jiaqun J Xu Xiao X Wang Junjiao J Wu Danya D Zhang Jiateng J Liu Juan J Xue Ziwei Z Zhan Guankai G Tan Bobby Cheng Peow BCP Chen Di D Chan Yun-Shen YS Ng Huck Hui HH Liu Wanlu W Hsu Chih-Hung CH Zhang Dan D Shen Yang Y Liang Hongqing H

Nature communications 20230620 1

Acquisition of new stem cell fates relies on the dissolution of the prior regulatory network sustaining the existing cell fates. Currently, extensive insights have been revealed for the totipotency regulatory network around the zygotic genome activation (ZGA) period. However, how the dissolution of the totipotency network is triggered to ensure the timely embryonic development following ZGA is largely unknown. In this study, we identify the unexpected role of a highly expressed 2-cell (2C) embry ...[more]

PMID: 37339952

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Project description:ImportanceCancer treatment delay is a recognized marker of worse outcomes. Timely treatment may be associated with physician patient-sharing network characteristics, yet this remains understudied.ObjectiveTo examine the associations of surgeon and care team patient-sharing network measures with breast cancer treatment delay.Design, setting, and participantsThis cross-sectional study of Medicare claims in a US population-based setting was conducted from 2017 to 2020. Eligible participants included patients with breast cancer who received surgery and the subset who went on to receive adjuvant therapy. Patient-sharing networks were constructed for treating physicians. Data were analyzed from September 2023 to February 2024.ExposuresSurgeon linchpin score (a measure of local uniqueness or scarcity) and care density (a measure of physician team familiarity) were assessed. Surgeons were considered linchpins if their linchpin score was in the top 15%. The care density of a patient's physician team was calculated on preoperative teams for surgically-treated patients and postoperative teams for adjuvant therapy-receiving patients.Main outcomes and measuresThe primary outcomes were surgical and adjuvant delay, which were defined as greater than 60 days between biopsy and surgery and greater than 60 days between surgery and adjuvant therapy, respectively.ResultsThe study cohort included 56 433 patients (18 004 aged 70-74 years [31.9%]) who were mostly from urban areas (44 931 patients [79.6%]). Among these patients, 8009 (14.2%) experienced surgical delay. Linchpin surgeon status (locally unique surgeon) was not statistically associated with surgical delay; however, patients with high preoperative care density (ie, high team familiarity) had lower odds of surgical delay compared with those with low preoperative care density (odds ratio [OR], 0.58; 95% CI, 0.53-0.63). Of the 29 458 patients who received adjuvant therapy after surgery, 5700 (19.3%) experienced adjuvant delay. Patients with a linchpin surgeon had greater odds of adjuvant delay compared with those with a nonlinchpin surgeon (OR, 1.30; 95% CI, 1.13-1.49). Compared with those with low postoperative care density, there were lower odds of adjuvant delay for patients with high postoperative care density (OR, 0.77; 95% CI, 0.69-0.87) and medium postoperative care density (OR, 0.85; 95% CI, 0.77-0.94).Conclusions and relevanceIn this cross-sectional study of Medicare claims, network measures capturing physician scarcity and team familiarity were associated with timely treatment. These results may help guide system-level interventions to reduce cancer treatment delays.

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Selective binding of retrotransposons by ZFP352 facilitates the timely dissolution of totipotency network.

Publications

Selective binding of retrotransposons by ZFP352 facilitates the timely dissolution of totipotency network.

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