CCAAT/Enhancer Binding Protein β inhibits myogenic differentiation via ID3

Abstract

Myogenesis is regulated by the coordinated expression of muscle regulatory factors, a family of transcription factors that includes MYOD, MYF5, myogenin and MRF4. Muscle regulatory factors are basic helix-loop-helix transcription factors that heterodimerize with E proteins to bind the regulatory regions of target genes. Their activity can be inhibited by members of the Inhibitor of DNA binding and differentiation (ID) family, which bind E-proteins with high affinity, thereby preventing muscle regulatory factor-dependent transcriptional responses. CCAAT/Enhancer Binding protein beta (C/EBPβ) is a transcription factor expressed in myogenic precursor cells that acts to inhibit myogenic differentiation, though the mechanism remains poorly understood. We identify Id3 as a novel C/EBPβ target gene that inhibits myogenic differentiation. Overexpression of C/EBPβ stimulates Id3 mRNA and protein expression, and is required for C/EBPβ-mediated inhibition of myogenic differentiation. Misexpression of C/EBPβ in myogenic precursors, such as in models of cancer cachexia, prevents the differentiation of myogenic precursors and we show that loss of Id3 rescues differentiation under these conditions, suggesting that the stimulation of Id3 expression by C/EBPβ is an important mechanism by which C/EBPβ inhibits myogenic differentiation.

20‐Hydroxyecdysone receptor‐activated Bombyx mori CCAAT/enhancer‐binding protein gamma regulates the expression of BmCBP and subsequent histone H3 lysine 27 acetylation in Bo. mori

“…However, whether homo/heterodimers of BmC/EBPg activate BmCBP expression requires further investigation. C/EBPs are also well-known CCAAT/EBPs and are widely reported to be involved in many cellular processes, such as cell growth and aging (Buck et al, 1999;Schafer et al, 2018), differentiation Radomska et al, 1998;AlSudais et al, 2018;Jeong et al, 2019), injury and inflammation response (Burgess-Beusse and Darlington, 1998;Poli, 1998;Jo et al, 2018), and cellular phenotypes (Lekstrom-Himes and Xanthopoulos, 1998;Salaroglio et al, 2018). In mammals, C/EBPs play pivotal roles in immunoresponse (Dai et al, 2017;Larabee et al, 2018), inflammatory response, liver regeneration, metabolism and numerous diseases (Ramji and Foka, 2002;Pulikkan et al, 2017;Wattanavanitchakorn et al, 2018).…”

Contaminating reactivity of a monoclonal CCAAT/Enhancer Binding Protein β antibody in differentiating myoblasts

“…1D). Since C/EBPb is an inhibitor of myogenesis 9,10 , the detection of the 23 kDa band correlates with myogenic differentiation (detected only in differentiating myoblasts) and not with C/EBPβ expression ( Fig 1C and D). The 23 kDa band was successfully precipitated using the anti-C/EBPb antibody but not by the control IgG as detected by silver staining ( Fig.…”

“…In healthy muscle, satellite cells express C/EBPb which inhibits myogenic differentiation 9,10 . Upon induction of differentiation, C/EBPβ expression dramatically decreases, allowing differentiation to proceed [9][10][11] . We observed that the anti-C/EBPb antibody (E299, ab32358) also detects myosin light chain 4 (MYL4) in differentiating myoblasts and in other cell lines.…”

Contaminating reactivity of a monoclonal CCAAT/Enhancer Binding Protein β antibody in differentiating myoblasts

“…to proceed [9][10][11] . We observed that the anti-C/EBP antibody (E299, ab32358) also detects myosin light chain 4 (MYL4) in differentiating myoblasts and in other cell lines.…”

“…In response to muscle injury, satellite cells become activated, proliferate, differentiate and fuse to form myofibers that express contractile proteins 8 . In healthy muscle, satellite cells express C/EBP which inhibits myogenic differentiation 9,10 .…”