The unique function of Runx1 in skeletal muscle differentiation and regeneration is mediated by an ETS interaction domain.

التفاصيل البيبلوغرافية
العنوان: The unique function of Runx1 in skeletal muscle differentiation and regeneration is mediated by an ETS interaction domain.
المؤلفون: Yu M, Thorner K, Parameswaran S, Wei W, Yu C, Lin X, Kopan R, Hass MR
المصدر: BioRxiv : the preprint server for biology [bioRxiv] 2023 Nov 21. Date of Electronic Publication: 2023 Nov 21.
نوع المنشور: Preprint
اللغة: English
بيانات الدورية: Country of Publication: United States NLM ID: 101680187 Publication Model: Electronic Cited Medium: Internet NLM ISO Abbreviation: bioRxiv Subsets: PubMed not MEDLINE
مستخلص: The conserved Runt-related (RUNX) transcription factor family are well-known master regulators of developmental and regenerative processes. Runx1 and Runx2 are both expressed in satellite cells (SC) and skeletal myotubes. Conditional deletion of Runx1 in adult SC negatively impacted self-renewal and impaired skeletal muscle maintenance. Runx1- deficient SC retain Runx2 expression but cannot support muscle regeneration in response to injury. To determine the unique molecular functions of Runx1 that cannot be compensated by Runx2 we deleted Runx1 in C2C12 that retain Runx2 expression and established that myoblasts differentiation was blocked in vitro due in part to ectopic expression of Mef2c, a target repressed by Runx1 . Structure-function analysis demonstrated that the Ets-interacting MID/EID region of Runx1, absent from Runx2, is critical to regulating myoblasts proliferation, differentiation, and fusion. Analysis of in-house and published ChIP-seq datasets from Runx1 (T-cells, muscle) versus Runx2 (preosteoblasts) dependent tissue identified enrichment for a Ets:Runx composite site in Runx1 -dependent tissues. Comparing ATACseq datasets from WT and Runx1KO C2C12 cells showed that the Ets:Runx composite motif was enriched in peaks open exclusively in WT cells compared to peaks unique to Runx1KO cells. Thus, engagement of a set of targets by the RUNX1/ETS complex define the non-redundant functions of Runx1 .
تواريخ الأحداث: Date Created: 20231204 Latest Revision: 20231204
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC10690193
DOI: 10.1101/2023.11.21.568117
PMID: 38045385
قاعدة البيانات: MEDLINE
الوصف
DOI:10.1101/2023.11.21.568117