Mycobacterium tuberculosis (MTB) infects 30% of all humans and kills someone every 20-30 s. Here we report genome-wide binding for ~80% of all predicted MTB transcription factors (TFs), and assayed global expression following induction of each TF. The MTB DNA-binding network consists of ~16,000 binding events from 154 TFs. We identify >50 TF-DNA consensus motifs and >1,150 promoter-binding events directly associated with proximal gene regulation. An additional ~4,200 binding events are in promoter windows and represent strong candidates for direct transcriptional regulation under appropriate environmental conditions. However, we also identify >10,000 'dormant' DNA-binding events that cannot be linked directly with proximal transcriptional control, suggesting that widespread DNA binding may be a common feature that should be considered when developing global models of coordinated gene expression.
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http://dx.doi.org/10.1038/ncomms6829 | DOI Listing |
Cell Commun Signal
January 2025
National Clinical Research Center for Child Health of Children's Hospital, Zhejiang University School of Medicine, Hangzhou, 310052, China.
CXXC type zinc finger protein 5 (CXXC5) is a member of the ZF-CXXC family and plays a pivotal role in signal integration and information transfer within cell signaling network. CXXC5 acts as a regulator in various physiological processes, and abnormalities in its protein structure or function have been linked to multiple pathological processes. In this article, we correspondingly describe the composition of the ZF-CXXC family, emphatically introducing the features of the CXXC5 gene and protein, review the role of CXXC5 in cellular signaling networks, the physiological and pathological processes associated with CXXC5 dysregulation, and particularly focus on the correlation between CXXC5 and cancers.
View Article and Find Full Text PDFAm J Hum Genet
January 2025
Institute of Human Genetics, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany; Institute of Human Genetics, University of Regensburg, 93053 Regensburg, Germany; Institute of Clinical Human Genetics, University Hospital Regensburg, 93053 Regensburg, Germany. Electronic address:
BCL11B is a Cys2-His2 zinc-finger (C2H2-ZnF) domain-containing, DNA-binding, transcription factor with established roles in the development of various organs and tissues, primarily the immune and nervous systems. BCL11B germline variants have been associated with a variety of developmental syndromes. However, genotype-phenotype correlations along with pathophysiologic mechanisms of selected variants mostly remain elusive.
View Article and Find Full Text PDFNAR Genom Bioinform
March 2025
National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi 110067, India.
Small proteins (≤100 amino acids) play important roles across all life forms, ranging from unicellular bacteria to higher organisms. In this study, we have developed SProtFP which is a machine learning-based method for functional annotation of prokaryotic small proteins into selected functional categories. SProtFP uses independent artificial neural networks (ANNs) trained using a combination of physicochemical descriptors for classifying small proteins into antitoxin type 2, bacteriocin, DNA-binding, metal-binding, ribosomal protein, RNA-binding, type 1 toxin and type 2 toxin proteins.
View Article and Find Full Text PDFDespite the sequencing revolution, large swaths of the genomes sequenced to date lack any information about the arrangement of transcription factor binding sites on regulatory DNA. Massively Parallel Reporter Assays (MPRAs) have the potential to dramatically accelerate our genomic annotations by making it possible to measure the gene expression levels driven by thousands of mutational variants of a regulatory region. However, the interpretation of such data often assumes that each base pair in a regulatory sequence contributes independently to gene expression.
View Article and Find Full Text PDFCancer Med
January 2025
Department of Gastroenterology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Suzhou, Jiangsu, People's Republic of China.
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