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Cis- and trans-regulatory mechanisms of gene expression in the ASJ sensory neuron of Caenorhabditis elegans.

ABSTRACT: The identity of a given cell type is determined by the expression of a set of genes sharing common cis-regulatory motifs and being regulated by shared transcription factors. Here, we identify cis and trans regulatory elements that drive gene expression in the bilateral sensory neuron ASJ, located in the head of the nematode Caenorhabditis elegans. For this purpose, we have dissected the promoters of the only two genes so far reported to be exclusively expressed in ASJ, trx-1 and ssu-1. We hereby identify the ASJ motif, a functional cis-regulatory bipartite promoter region composed of two individual 6 bp elements separated by a 3 bp linker. The first element is a 6 bp CG-rich sequence that presumably binds the Sp family member zinc-finger transcription factor SPTF-1. Interestingly, within the C. elegans nervous system SPTF-1 is also found to be expressed only in ASJ neurons where it regulates expression of other genes in these neurons and ASJ cell fate. The second element of the bipartite motif is a 6 bp AT-rich sequence that is predicted to potentially bind a transcription factor of the homeobox family. Together, our findings identify a specific promoter signature and SPTF-1 as a transcription factor that functions as a terminal selector gene to regulate gene expression in C. elegans ASJ sensory neurons.

SUBMITTER: Gonzalez-Barrios M

PROVIDER: S-EPMC4423358 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature

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Cis- and trans-regulatory mechanisms of gene expression in the ASJ sensory neuron of Caenorhabditis elegans.

González-Barrios María M Fierro-González Juan Carlos JC Krpelanova Eva E Mora-Lorca José Antonio JA Pedrajas José Rafael JR Peñate Xenia X Chavez Sebastián S Swoboda Peter P Jansen Gert G Miranda-Vizuete Antonio A

Genetics 20150312 1

The identity of a given cell type is determined by the expression of a set of genes sharing common cis-regulatory motifs and being regulated by shared transcription factors. Here, we identify cis and trans regulatory elements that drive gene expression in the bilateral sensory neuron ASJ, located in the head of the nematode Caenorhabditis elegans. For this purpose, we have dissected the promoters of the only two genes so far reported to be exclusively expressed in ASJ, trx-1 and ssu-1. We hereby ...[more]

PMID: 25769980

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Project description:Anatomically and functionally defined neuron types are sometimes further classified into individual subtypes based on unique functional or molecular properties. To better understand how developmental programs controlling neuron type specification are mechanistically linked to programs controlling neuronal subtype specification, we have analyzed a neuronal subtype specification program that occurs across the left/right axis in the nervous system of the nematode C. elegans. A terminal selector transcription factor, CHE-1, is required for the specification of the ASE neuron class, and a gene regulatory feedback loop of transcription factors and miRNAs is required to diversify the two ASE neurons into an asymmetric left and right subtype (ASEL and ASER). However, the link between the CHE-1-dependent ASE neuron class specification and the ensuing left-right subtype specification program is poorly understood. We show here that CHE-1 has genetically separable functions in controlling bilaterally symmetric ASE neuron class specification and the ensuing left-right subtype specification program. Both neuron class specification and asymmetric subclass specification depend on CHE-1-binding sites (;ASE motifs') in symmetrically and asymmetrically expressed target genes, but in the case of asymmetrically expressed target genes, the activity of the ASE motif is modulated through a diverse set of additional cis-regulatory elements. Depending on the target gene, these cis-regulatory elements either promote or inhibit the activity of CHE-1. The activity of these L/R asymmetric cis-regulatory elements is indirectly controlled by che-1 itself, revealing a feed-forward loop configuration in which che-1 restricts its own activity. Relative binding affinity of CHE-1 to ASE motifs also depends on whether a gene is expressed bilaterally or in a left/right asymmetric manner. Our analysis provides insights into the molecular mechanisms of neuronal subtype specification, demonstrating that the activity of a neuron type-specific selector gene is modulated by a variety of distinct means to diversify individual neuron classes into specific subclasses. It also suggests that feed-forward loop motifs may be a prominent feature of neuronal diversification events.

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Dataset Information

Cis- and trans-regulatory mechanisms of gene expression in the ASJ sensory neuron of Caenorhabditis elegans.

Publications

Cis- and trans-regulatory mechanisms of gene expression in the ASJ sensory neuron of Caenorhabditis elegans.

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