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Synthetic transcription factors establish the function of nine amino acid transactivation domains of Komagataella phaffii Mxr1.
J Biol Chem
January 2025
Department of Biochemistry, Indian Institute of Science, Bangalore 560012, INDIA. Electronic address:
The zinc finger transcription factor Mxr1 (methanol expression regulator 1) of the methylotrophic yeast Komagataella phaffii (formerly Pichia pastoris) harbors a DNA-binding domain (DBD) consisting of two CH zinc fingers (Mxr1ZF) between amino acids 36-101 and a previously identified nine amino acid transactivation domain (9aaTAD) between residues 365-373 (TAD A, QELESSLNA). Beyond this, 21 putative 9aaTADs (designated TAD B-V) located between amino acids 401-1155 remain to be characterized. Here, we demonstrate that a compact synthetic transcription factor composed of Mxr1ZF and three tandem copies of TAD A can activate the transcription of Mxr1 target genes for ethanol and methanol metabolism with specificity and efficiency comparable to the full-length protein.
View Article and Find Full Text PDFImpacts of on oxygen sensitivity, gene expression, and murine infection in 630∆.
J Bacteriol
January 2025
Department of Medicine, Division of Gastroenterology and Hepatology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA.
infection (CDI), characterized by colitis and diarrhea, afflicts approximately half a million people in the USA every year, burdening both individuals and the healthcare system. 630Δ is an erythromycin-sensitive variant of the clinical isolate 630 and is commonly used in the research community due to its genetic tractability. 630Δ possesses a point mutation in , an autoregulated transcriptional repressor that regulates oxidative stress resistance genes.
View Article and Find Full Text PDFUnlabelled: is one of the three most frequently mutated genes in age-related clonal hematopoiesis (CH), alongside and . CH can progress to myeloid malignancies including chronic monomyelocytic leukemia (CMML), and is also strongly associated with inflammatory cardiovascular disease and all-cause mortality in humans. DNMT3A and TET2 regulate DNA methylation and demethylation pathways respectively, and loss-of-function mutations in these genes reduce DNA methylation in heterochromatin, allowing de-repression of silenced elements in heterochromatin.
View Article and Find Full Text PDFMolecular mechanisms underlying allosteric behavior of Escherichia coli DgoR, a GntR/FadR family transcriptional regulator.
Nucleic Acids Res
January 2025
Department of Biological Sciences, Indian Institute of Science Education and Research (IISER) Mohali, Sector 81, Knowledge City, SAS Nagar, Mohali 140306, Punjab, India.
GntR/FadR family featuring an N-terminal winged helix-turn-helix DNA-binding domain and a C-terminal α-helical effector-binding and oligomerization domain constitutes one of the largest families of transcriptional regulators. Several GntR/FadR regulators govern the metabolism of sugar acids, carbon sources implicated in bacterial-host interactions. Although effectors are known for a few sugar acid regulators, the unavailability of relevant structures has left their allosteric mechanism unexplored.
View Article and Find Full Text PDFDeletion of Ovary-Specific Transcript Causes Dysfunction of Meiosis and Derepress of DNA Transposons in Zebrafish Ovaries.
Biology (Basel)
December 2024
Key Laboratory of Breeding Biotechnology and Sustainable Aquaculture, Institute of Hydrobiology, Hubei Hongshan Laboratory, Chinese Academy of Sciences, Wuhan 430072, China.
Alternative splicing of (DEAD-box helicase 4), a key germline marker gene, has been reported to generate sex-specific transcripts in zebrafish gonads. The biological functions and regulatory mechanisms of the ovary-specific transcript () during oogenesis remain unclear. In this study, we found that mutants, in which was specifically deleted, had enlarged ovaries but laid fewer eggs, along with having a lower fertilization rate compared to WT controls.
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