DNTTIP1 Knockout 786-O Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population engineered from the 786-O human clear cell renal carcinoma line, with targeted disruption of the DNTTIP1 gene. This polyclonal format provides a genetically diverse knockout model for studying DNTTIP1 function without clonal bias, suitable for ribosome biogenesis and cancer research.
The 786-O host line is a VHL-deficient clear cell renal cell adenocarcinoma model originating from a primary tumor, characterized by constitutive HIF activation under normoxia. This pseudo-hypoxic state drives angiogenesis and tumor progression, making it a standard platform for investigating hypoxia signaling and its crosstalk with nucleolar processes.
DNTTIP1 is a transcriptional corepressor that silences ribosomal DNA (rDNA) transcription by recruiting the NoRC complex, interacting with TIP5, HDAC1, and SMARCA5 to promote histone deacetylation and chromatin compaction. It is regulated by ESR1, Sp1, and mTOR signaling and represses RNA polymerase I activity, reducing 45S pre-rRNA synthesis. DNTTIP1 also associates with DNTT, UBF, and core factors POLR1A and RRN3, integrating growth factor and estrogen receptor pathways to control ribosome biogenesis, nucleolar stress responses, and chromatin remodeling.
In VHL-null 786-O cells, constitutive HIF activation imposes high protein synthesis demands, potentially reliant on ribosome biogenesis. DNTTIP1 knockout may relieve rDNA silencing, elevating pre-rRNA levels and altering nucleolar dynamics, offering a model to study how derepressed ribosome production affects proliferation, apoptosis, and hypoxic adaptation in renal cancer. It also enables exploration of estrogen receptor?Cnucleolar crosstalk in a pseudohypoxic tumor context.
Applications include RT-qPCR and RNA-seq for pre-rRNA quantification, ChIP-qPCR to assess rDNA chromatin state, western blotting and immunofluorescence for nucleolar markers UBF and fibrillarin, and functional assays for proliferation, apoptosis, and nucleolar stress. The polyclonal population supports chromatin remodeling studies and drug discovery efforts targeting hypoxia?Cribosome biogenesis crosstalk in renal cell carcinoma. For inquiries, please contact Ascent Research.
