Mechanisms Underlying Hox-Mediated Transcriptional Outcomes [PDF]
Frontiers in Cell and Developmental Biology, 2021 Metazoans differentially express multiple Hox transcription factors to specify diverse cell fates along the developing anterior-posterior axis. Two challenges arise when trying to understand how the Hox transcription factors regulate the required target ...
Brittany Cain +2 more
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Decoding the mechanisms of cooperative DNA binding by the Paired-like homeodomain family [PDF]
Nature CommunicationsThe 36 Paired-like homeodomain transcription factors in humans are required for the development of many cell types, tissues, and organs as missense variants in 24 Paired-like genes have been associated with numerous diseases and developmental disorders ...
Brittany Cain +3 more
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Enhancers with cooperative Notch binding sites are more resistant to regulation by the Hairless co-repressor. [PDF]
PLoS Genetics, 2021 Notch signaling controls many developmental processes by regulating gene expression. Notch-dependent enhancers recruit activation complexes consisting of the Notch intracellular domain, the Cbf/Su(H)/Lag1 (CSL) transcription factor (TF), and the ...
Yi Kuang +11 more
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A Drosophila Su(H) model of Adams-Oliver Syndrome reveals cofactor titration as a mechanism underlying developmental defects. [PDF]
PLoS Genetics, 2022 Notch signaling is a conserved pathway that converts extracellular receptor-ligand interactions into changes in gene expression via a single transcription factor (CBF1/RBPJ in mammals; Su(H) in Drosophila).
Ellen K Gagliani +12 more
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The ALX4 dimer structure provides insight into how disease alleles impact function [PDF]
Nature CommunicationsHow homeodomain proteins gain sufficient DNA binding specificity to regulate diverse processes is a long-standing question. Here, we determine how the ALX4 Paired-like protein achieves DNA binding specificity for a TAAT–NNN–ATTA dimer site. We first show
Brittany Cain +4 more
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A Hox complex activates and potentiates the Epidermal Growth Factor signaling pathway to specify Drosophila oenocytes. [PDF]
PLoS Genetics, 2017 Hox transcription factors specify distinct cell types along the anterior-posterior axis of metazoans by regulating target genes that modulate signaling pathways. A well-established example is the induction of Epidermal Growth Factor (EGF) signaling by an
Guolun Wang +3 more
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Gli3 utilizes Hand2 to synergistically regulate tissue-specific transcriptional networks [PDF]
eLife, 2020 Despite a common understanding that Gli TFs are utilized to convey a Hh morphogen gradient, genetic analyses suggest craniofacial development does not completely fit this paradigm.
Kelsey H Elliott +12 more
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Enhancer architecture sensitizes cell specific responses to Notch gene dose via a bind and discard mechanism [PDF]
eLife, 2020 Notch pathway haploinsufficiency can cause severe developmental syndromes with highly variable penetrance. Currently, we have a limited mechanistic understanding of phenotype variability due to gene dosage.
Yi Kuang +15 more
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Defective Notch1 signaling in endothelial cells drives pathogenesis in a mouse model of Adams-Oliver syndrome [PDF]
The Journal of Clinical InvestigationAdams-Oliver syndrome (AOS) is a rare congenital disorder characterized by scalp, limb, and cardiovascular defects. Although variants in the NOTCH1 receptor, DLL4 ligand, and RBPJ transcription factor have been implicated in AOS, the driving tissue types
Alyssa F. Solano +15 more
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Degenerate Pax2 and Senseless binding motifs improve detection of low-affinity sites required for enhancer specificity. [PDF]
PLoS Genetics, 2018 Cells use thousands of regulatory sequences to recruit transcription factors (TFs) and produce specific transcriptional outcomes. Since TFs bind degenerate DNA sequences, discriminating functional TF binding sites (TFBSs) from background sequences ...
Arya Zandvakili +4 more
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