CTCF Represses CIB2 to Balance Proliferation and Differentiation of Goat Myogenic Satellite Cells via Integrin α7β1–PI3K/AKT Axis

Skeletal muscle development is a critical economic trait in livestock, governed by myogenic satellite cell regulation. Integrins mediate mechanical anchorage to the ECM and enable ECM-intracellular signaling. <i>CIB2</i>, as an EF-hand-domain protein involved in mechanotransduction, shows significant developmental regulation in goat muscle. Although the role of <i>CIB2</i> in skeletal muscle growth is poorly characterized, we observed pronounced developmental upregulation of <i>IB2</i> in postnatal goat muscle. <i>CIB2</i> expression increased >20-fold by postnatal day 90 (P90) compared to P1, sustaining elevation through P180 (<i>p</i> < 0.05). Functional investigations indicated that siRNA-mediated knockdown of <i>CIB2</i> could inhibit myoblast proliferation by inducing S-phase arrest (<i>p</i> < 0.05) and downregulating the expression of <i>CDK4</i>/<i>Cyclin D</i>/<i>E</i>. Simultaneously, <i>CIB2</i> interference treatment was found to decrease the proliferative activity of goat myogenic satellite cells, yet it significantly promoted differentiation by upregulating the expression of <i>MyoD</i>/<i>MyoG</i>/<i>MyHC</i> (<i>p</i> < 0.01). Mechanistically, <i>CTCF</i> was identified as a transcriptional repressor binding to an intragenic region of the <i>CIB2</i> gene locus (ChIP enrichment: 2.3-fold, <i>p</i> < 0.05). Knockdown of <i>CTCF</i> induced upregulation of <i>CIB2</i> (<i>p</i> < 0.05). RNA-seq analysis established <i>CIB2</i> as a calcium signaling hub: its interference activated IL-17/TNF and complement cascades, while overexpression suppressed focal adhesion/ECM-receptor interactions and enriched neuroendocrine pathways. Collectively, this study identifies the CTCF-CIB2-integrin α7β1-PI3K/AKT axis as a novel molecular mechanism that regulates the balance of myogenic fate in goats. These findings offer promising targets for genomic selection and precision breeding strategies aimed at enhancing muscle productivity in ruminants.