CBF beta and the Leukemogenic Fusion Protein CBF beta-SMMHC Associate With Mitotic Chromosomes to Epigenetically Regulate Ribosomal Genes

作者：Lopez Camacho Cesar; van Wijnen Andre J; Lian Jane B; Stein Janet L; Stein Gary S^*

来源：Journal of Cellular Biochemistry, 2014, 115(12): 2155-2164.

DOI：10.1002/jcb.24892

• LEUKEMIA
• EPIGENETICS
• RIBOSOMAL RNA (rRNA)
• TRANSCRIPTION COACTIVATORS
• CORE BINDING FACTOR
• MITOTIC BOOKMARKING
• RIBOSOMAL GENE EXPRESSION

Mitotic bookmarking is an epigenetic control mechanism that sustains gene expression in progeny cells; it is often found in genes related to the maintenance of cellular phenotype and growth control. RUNX transcription factors regulate a broad spectrum of RNA Polymerase (Pol II) transcribed genes important for lineage commitment but also regulate RNA Polymerase I (Pol I) driven ribosomal gene expression, thus coordinating control of cellular identity and proliferation. In this study, using fluorescence microscopy and biochemical approaches we show that the principal RUNX co-factor, CBF, associates with nucleolar organizing regions (NORs) during mitosis to negatively regulate RUNX-dependent ribosomal gene expression. Of clinical relevance, we establish for the first time that the leukemogenic fusion protein CBF-SMMHC (smooth muscle myosin heavy chain) also associates with ribosomal genes in interphase chromatin and mitotic chromosomes to promote and epigenetically sustain regulation of ribosomal genes through RUNX factor interactions. Our results demonstrate that CBF contributes to the transcriptional regulation of ribosomal gene expression and provide further understanding of the epigenetic role of CBF-SMMHC in proliferation and maintenance of the leukemic phenotype. J. Cell. Biochem. 115: 2155-2164, 2014.

• 出版日期2014-12