Kobia F Duchi S Deflorian G Vaccari T

Molecular oncology

2014-03-01

Tognon E Kobia F Busi I Fumagalli A De Masi F Vaccari T

Autophagy

2016-01-01

Francis Kobia Jesse Gitaka Francis Makokha Moses Kamita Joshua Kibera Cynthia Mwenda Gladys Mucee Bactrin Kilingo

2019-12-03

Francis Kobia Jesse Gitaka

2020-04-17

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AbstractCooperative DNA binding is a key feature of transcriptional regulation. Here we examined the role of cooperativity in Notch signaling by CRISPR-mediated engineering of mice in which neither Notch1 nor Notch2 can homo- or heterodimerize, essential for cooperative binding to sequence paired sites (SPS) located near many Notch-regulated genes. While most known Notch-dependent phenotypes were unaffected in Notch1/2 dimer-deficient mice, a subset of tissues proved highly sensitive to loss of cooperativity. These phenotypes include heart development, compromising viability in combination with low gene dose, and the gut, developing ulcerative colitis in response to 1% DSS. The most striking phenotypes – gender imbalance and splenic marginal zone B cell lymphoma – emerged in combination with dose reduction or when challenged by chronic fur mite infestation. This study highlights the role of the environment in malignancy and colitis, and is consistent with Notch-dependent anti-parasite immune responses being compromised in the dimer deficient animals.HighlightsNotch dimerization has an in vivo role in contributing to intestinal homeostasisLoss of cooperativity can manifest as Notch gain or loss of function phenotypesMite infestation exacerbates all phenotypes, triggers MZB hyperproliferation in mutant animalsMite-infested mutant mice develop SMZL with age

2020-03-06

Francis M. Kobia Kaushik Maiti Moses M. Obimbo Roger Smith Jesse Gitaka

Trends in Parasitology

2022-05-01

PLOS Biology

2020-10-05