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Nature's Imitation Game: Decipher the Combinatorial CTD Code for Eukaryotic Transcription
Author(s) -
Zhang Y. Jessie
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.265.1
Subject(s) - ctd , rna polymerase ii , biology , transcription (linguistics) , computational biology , heptad repeat , eukaryotic transcription , microbiology and biotechnology , transcription factor , genetics , gene , gene expression , promoter , peptide sequence , linguistics , oceanography , philosophy , geology
In eukaryotes, the C‐terminal domain of RNA polymerase II (CTD) orchestrates the temporal and spatial control of transcription and is involved in the epigenetic regulation of gene expression. Errors in CTD regulation can result in cell death, cancer and severe developmental defects. The CTD executes its function as a transcription template to recruite transcription regulators through various post‐translational modifications on its heptad repeats. Recently, novel modifications on CTD have been identified, setting the stage for the possibility of combinatorial mechanisms for transcription regulation. We focused on the eukaryotic phosphatases in the CTD regulation and how they affect the function of CTD binding proteins. Determination of the structures of these CTD phosphatases guide our structure‐function investigation. Using a collection of chemical biology techniques including analytical chemistry, spectroscopy, enzymology and structural biology, we dissect the multiple layers of regulation in CTD‐mediated transcription. In particular, we developed an innovative method of mass spectromety, Ultraviolet photodissociation (UVPD), to map the site of modification in S. cerevisiae and Drosophila CTDs. Overall, we probe how the identities and phosphorylation states of individual residues in the consensus heptad repeats of CTD result in differentiated post‐translational modification states within CTD that lead to various transcription outcomes. Support or Funding Information The work is funded by National Institute for Health, Welch Foundation and Alzheimer's Drug Discovery Foundation.