Unravelling the knotty process of gene expression
By Elena E. Giorgi
Computational Biologist, Los Alamos National Laboratory
From the beginning of a project looking at three genetically identical mice that did not look the same, Karissa Sanbonmatsu was obsessed by one question: What distinguishes life from matter?
Karissa Sanbonmatsu, et al
While it is well-recognized that chromatin loops play an important role in gene regulation, structural details regarding higher order chromatin loops are only emerging. Here we present a systematic study of restrained chromatin loops ranging from 25 to 427 nucleosomes (fibers of 5–80 Kb DNA in length), mimicking gene elements studied by 3C contact data. We find that hierarchical looping represents a stable configuration that can effectively bring distant regions of the GATA-4 gene together, satisfying connections reported by 3C experiments. Additionally, we find that restrained chromatin fibers larger than 100 nucleosomes (∼20Kb) form closed plectonemes, whereas fibers shorter than 100 nucleosomes form simple hairpin loops. By studying the dependence of loop structures on internal parameters, we show that loop features are sensitive to linker histone concentration, loop length, divalent ions, and DNA linker length.
KY Sanbonmatsu, et al
Until recently, engineering strategies for altering gene expression have focused on transcription control using strong inducible promoters or one of several methods to knock down wasteful genes. Recently, synthetic riboregulators have been developed for translational regulation of gene expression. Here, we report a new modular synthetic riboregulator class that has the potential to finely tune protein expression and independently control the concentration of each enzyme in an engineered metabolic pathway. This development is important because the most straightforward approach to altering the flux through a particular metabolic step is to increase or decrease the concentration of the enzyme.
The Biology of Gender, from DNA to the Brain
How does gender work? It's not just about our chromosomes, says biologist Karissa Sanbonmatsu. In this TEDWomen talk, she shares new discoveries from epigenetics, the emerging study of how DNA activity can permanently change based on social factors like trauma or diet.
How You Know You're in Love: Epigenetics, Stress & Gender Identity
Social interactions alter DNA (‘epigenetics’). Revealing how her own gender transition led her down the path of epigenetics, Scientist Karissa Sanbonmatsu takes us on a journey to DNA rave parties and the science of love.
With her team, Sanbonmatsu uses computational and experimental approaches to understand the mechanism of a diverse array of non-coding RNA systems.