5w9s
Zinc finger of human CXXC5 in complex with CpG DNA
Structural highlights
FunctionCXXC5_HUMAN May indirectly participate in activation of the NF-kappa-B and MAPK pathways. Acts as a mediator of BMP4-mediated modulation of canonical Wnt signaling activity in neural stem cells (By similarity). Required for DNA damage-induced ATM phosphorylation, p53 activation and cell cycle arrest. Involved in myelopoiesis. Transcription factor. Binds to the oxygen responsive element of COX4I2 and represses its transcription under hypoxia conditions (4% oxygen), as well as normoxia conditions (20% oxygen) (PubMed:23303788). May repress COX4I2 transactivation induced by CHCHD2 and RBPJ (PubMed:23303788).[1] [2] [3] Publication Abstract from PubMedThe CXXC domain, first identified as the reader of unmodified CpG dinucleotide, plays important roles in epigenetic regulation by targeting various activities to CpG islands. Here we systematically measured and compared the DNA-binding selectivities of all known human CXXC domains by different binding assays, and complemented the existing function-based classification of human CXXC domains with a classification based on their DNA selectivities. Through a series of crystal structures of CXXC domains with DNA ligands, we unravel the molecular mechanisms of how these CXXC domains, including single CXXC domains and tandem CXXC-PHD domains, recognize distinct DNA ligands, which further supports our classification of human CXXC domains and also provides insights into selective recruitment of chromatin modifiers to their respective targets via CXXC domains recognizing different genomic DNA sequences. Our study facilitates the understanding of the relationship between the DNA-binding specificities of the CXXC proteins and their biological functions. DNA Sequence Recognition of Human CXXC Domains and Their Structural Determinants.,Xu C, Liu K, Lei M, Yang A, Li Y, Hughes TR, Min J Structure. 2017 Dec 16. pii: S0969-2126(17)30396-9. doi:, 10.1016/j.str.2017.11.022. PMID:29276034[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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