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Jorda-Llorens, J. I.

Publications and source records attributed to Jorda-Llorens, J. I..

2 recordsLinked to original sources

CUT homeobox factors modulate chromatin accessibility in neurons

Neuronal identity relies on coordinated transcriptional programs that include both neuron type-specific features and broadly shared pan-neuronal properties. While transcription factors that control neuronal gene expression have been defined, how these regulators interface with chromatin accessibility at neuronal loci remains poorly understood. CUT homeobox factors are broadly expressed in the C. elegans nervous system and provide a genetically defined system to examine transcription factor associated chromatin accessibility in neurons. Here, we establish a fluorescence-activated sorting workflow to enrich neuronal nuclei using a pan-neuronal nuclear marker and apply bulk ATAC-seq to profile chromatin accessibility in wild-type and CUT mutant animals. We identify CUT-dependent accessibility differences in neuronal nuclei, with changes concentrated at promoter-proximal regions and linked to neuronal genes, including neuronally enriched and pan-neuronal categories. Together, this work provides in vivo neuronal chromatin accessibility profiles and defines CUT-dependent changes at a subset of neuronal regulatory regions.

neuroscience↗

Alternative splicing controls pan-neuronal homeobox gene expression

The pan-neuronally expressed and phylogenetically conserved CUT homeobox gene ceh-44/CUX orchestrates pan-neuronal gene expression throughout the nervous system of C. elegans. As in many other species, including humans, ceh-44/CUX is encoded by a complex locus that also codes for a Golgi-localized protein. How gene expression from this complex locus is controlled and, in C. elegans, directed to all cells of the nervous system has not been investigated. We show here that pan-neuronal expression of CEH-44/CUX is controlled by a pan-neuronal RNA splicing factor, UNC-75/CELF, the C. elegans homolog of vertebrate CELF proteins. UNC-75/CELF temporally and spatially specifies the production of an alternative, CEH-44/CUX homeobox gene-encoding transcript from a ubiquitously expressed gene locus, which also produces a Golgi apparatus-localized golgin protein, CONE-1 ("CASP of nematodes"). During embryogenesis the cone-1/ceh-44 locus exclusively produces the Golgi-localized CONE-1/CASP protein in all tissues, but upon the onset of postmitotic terminal differentiation of neurons, UNC-75/CELF induces the production of the alternative CEH-44/CUX CUT homeobox gene-encoding transcript, exclusively in the nervous system. Hence, UNC-75/CELF-mediated alternative splicing not only directs pan-neuronal gene expression, but also excludes a phylogenetically deeply conserved golgin from the nervous system, paralleling surprising spatial specificities of another golgin that we describe here as well. In summary, our findings provide novel insights into how all cells in a nervous system acquire pan-neuronal identity features.

developmental biology↗