A C/EBPβ Isoform Recruits the SWI/SNF Complex to Activate Myeloid Genes

Abstract

The activation of many genes requires the concerted effort of two or more transcription factors. Although C/EBP beta is known to cooperate with Myb to induce transcription of the granulocyte-specific mim-1 gene, the molecular mechanism of this cooperativity is undefined. We show that the N terminus of the full-length C/EBP beta isoform, which is essential for induction of the mim-1 gene in chromatin, interacts specifically with the SWI/SNF complex. Grafting this domain onto Myb generates a chimeric activator that recruits SWI/SNF and induces mim-1 transcription in the absence of C/EBP beta. Interaction between C/EBP beta and SWI/SNF is essential for activating a subgroup of resident target genes in chromatin and may represent a major determinant of combinatorial gene regulation in eukaryotes.

The requirement for SNF5/INI1 in adipocyte differentiation highlights new features of malignant rhabdoid tumors

“…ChIP assays further document that this activation is associated with a binding of hSNF5/INI1 and C/EBPb at the endogenous promoter. The current model proposes that C/EBPb binds the PPARg2 promoter, and then recruits SWI/SNF, the ATPase activity of which is required for transcription activation (Kowenz-Leutz and Leutz, 1999;Salma et al, 2004). Our results further indicate that, in MRTs, C/EBPb binding at the PPARg2 promoter is achieved in the absence of hSNF5/INI1 but that PPARg2 induction only occurs upon hSNF5/INI1 binding.…”

Geminin's Double Life: Chromatin Connections that Regulate Transcription at the Transition from Proliferation to Differentiation

“…Blocking Brg1 or SWI/SNF activity interferes with differentiation in retinal, myeloid, muscle, adipocyte, enterocyte, erythrocyte and neuronal cells. 31,[74][75][76][77][78][79][80] Together, the observations above suggest that the antagonistic interactions between Geminin and SWI/SNF that we have observed during neurogenesis could also regulate the proliferative-differentiative transition in other cellular contexts. Effects of both Geminin and SWI/SNF in regulating the proliferation to differentiation transition intersect with many other critical cell cycle and transcriptional control systems in a complex manner.…”

CCAAT/enhancer binding protein beta (C/EBPβ)-2 transforms normal mammary epithelial cells and induces epithelial to mesenchymal transition in culture

“…They demonstrated that C/EBPb-1 (termed LAP* in their work) interacts with the SWI/SNF chromatin remodelling complex, whereas C/EBPb-2 (LAP) does not. Interestingly, the N-terminal 21 amino acids of LAP* were shown to be essential, although not sufficient, for recruitment of the SWI/SNF complex (Kowenz-Leutz and Leutz, 1999). We have previously observed a striking difference in the expression profiles of C/EBPb-1 and -2 in normal versus neoplastic human mammary epithelial cells derived from both primary tissues and established cell lines (Eaton et al, 2001).…”

“…Although C/EBPb-1 and -2 differ by only 23 amino acids in humans (21 amino acids in rodents), our laboratory and others have observed functional differences between these two activating isoforms. Kowenz-Leutz and Leutz (1999) reported that only the largest C/EBPb isoform is able to cooperate with Myb to activate the mim-1 gene and other myeloid-specific genes in chromatin. They demonstrated that C/EBPb-1 (termed LAP* in their work) interacts with the SWI/SNF chromatin remodelling complex, whereas C/EBPb-2 (LAP) does not.…”