Mouse anti-Human CNOT2 polyclonal antibody

The multi-subunit CCR4 (carbon catabolite repressor 4)-NOT (Negative on TATA) complex serves as a central coordinator of all different steps of eukaryotic gene expression. Here we performed a systematic and comparative analysis of cells where the CCR4-NOT subunits CNOT1, CNOT2 or CNOT3 were individually downregulated using doxycycline-inducible shRNAs. Microarray experiments showed that downregulation of either CNOT subunit resulted in elevated expression of major histocompatibility complex class II (MHC II) genes which are found in a gene cluster on chromosome 6. Increased expression of MHC II genes after knock-down or knock-out of either CNOT subunit was seen in a variety of cell systems and also in naive macrophages from CNOT3 conditional knock-out mice. CNOT2-mediated repression of MHC II genes occurred also in the absence of the master regulator class II transactivator (CIITA) and did not cause detectable changes of the chromatin structure at the chromosomal MHC II locus. CNOT2 downregulation resulted in an increased de novo transcription of mRNAs whereas tethering of CNOT2 to a regulatory region governing MHC II expression resulted in diminished transcription. These results expand the known repertoire of CCR4-NOT members for immune regulation and identify CNOT proteins as a novel group of corepressors restricting class II expression.

Only a few individuals with 12q15 deletion have been described, presenting with a disorder characterized by learning disability, developmental delay, nasal speech, and hypothyroidism. The smallest region of overlap for this syndrome was included in a genomic segment spanning CNOT2, KCNMB4, and PTPRB genes. We report on an additional patient harboring a 12q15 microdeletion encompassing only part of CNOT2 gene, presenting with a spectrum of clinical features overlapping the 12q15 deletion syndrome phenotype. We propose CNOT2 as the phenocritical gene for 12q15 deletion syndrome and its haploinsufficiency being associated with an autosomal dominant disorder, presenting with developmental delay, hypotonia, feeding problems, learning difficulties, nasal speech, skeletal anomalies, and facial dysmorphisms.