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Helen M Chamberlin

Publications and source records attributed to Helen M Chamberlin.

9 recordsLinked to original sources
PubMed2006

Pax2/5/8 proteins promote cell survival in C. elegans.

Programmed cell death, or apoptosis, plays an important role during normal development, and is disrupted in a range of disease states. Although the key molecular events that occur during apoptosis are well characterized, less is known about the regulatory inputs that influence whether a cell will live or die. Work in mouse and human cells has shown that Pax transcription factors can influence cell death and promote cell survival, but the mechanism for their activity is not clear. Here, we show that two Pax2/5/8-related genes (egl-38 and pax-2) influence both somatic and germline cell death in C. elegans. Using genetic and molecular experiments, we show that the Pax proteins act as transcriptional regulators of ced-9, the C. elegans bcl-2 gene. These results identify a mechanism for Pax2/5/8-mediated regulation of cell death, and underscore the importance of transcriptional regulation of core apoptotic pathway genes in influencing cell survival.

Animals↗
PubMed2006

The Pax2/5/8 gene egl-38 coordinates organogenesis of the C. elegans egg-laying system.

Organogenesis requires coordinated development between different tissues and cells. The Pax family of transcription factors coordinates multiple developmental events in organs including the kidney, thyroid and the eye. Studying Pax factors in different organisms should identify unifying characteristics of organ development with implications to both development and disease. Here we investigate the function of the Pax2/5/8 transcription factor EGL-38 in coordinating development of the C. elegans egg-laying system. A functional egg-laying system requires cell fate specification events in the epithelial cells of the vulva as well as the mesodermal cells in the uterus of the somatic gonad. Using gene expression studies, genetic mutant analysis and genetic mosaics, we show that egl-38 has functions in both tissues of the organ to promote its development. We incorporate these results together with previous results to propose that EGL-38 plays multiple roles in the development of the egg-laying system, acting to both promote cell fate and to coordinate the development between different cell types. As the Pax2 gene performs similar roles in the development of the mammalian kidney, we show that coordinating organogenesis is a conserved function for Pax2/5/8 transcription factors.

Amino Acid Sequence↗
PubMed2005

The bZip proteins CES-2 and ATF-2 alter the timing of transcription for a cell-specific target gene in C. elegans.

The Caenorhabditis elegans basic leucine zipper (bZip) protein CES-2 regulates the transcription of different genes in different cells. Here, we show that CES-2 mediates its effects in one cell (the excretory duct cell) together with another bZip protein, ATF-2. Both proteins influence transactivation of a target gene, lin-48. Although lin-48 is required for both anatomical and physiological features of the excretory duct cell, ces-2 and atf-2 mutants only exhibit anatomical defects. We show that CES-2 and ATF-2 modify the temporal transcription of lin-48, acting to initiate embryonic expression required for normal excretory system development and anatomy. In contrast, CES-2 and ATF-2 do not influence post-embryonic lin-48 expression. We provide evidence that CES-2 and ATF-2 can interact with each other, and that they cooperate to form a complex on lin-48 regulatory sequences. Thus, the two bZip proteins function together as one of several inputs that influence the spatial and temporal regulation of lin-48.

Activating Transcription Factor 2↗
PubMed2005

Alteration of the DNA binding domain disrupts distinct functions of the C. elegans Pax protein EGL-38.

The paired-domain-containing Pax transcription factors play an important role in the development of a range of organ, tissue and cell types. Although DNA binding elements and target genes for Pax proteins have been identified, how these proteins identify appropriate DNA elements and regulate different genes in different cellular contexts is not well understood. To investigate the relationship between Pax proteins and their targets, we have studied the in vivo and in vitro properties associated with wild-type and different mutant variants of the Caenorhabditis elegans Pax protein EGL-38. Here, we characterize the properties of four mutations that result in an amino acid substitution in the DNA binding domain of EGL-38. We find that animals bearing the different mutant alleles exhibit tissue-preferential defects in egl-38 function. The mutant proteins are also altered in their activity in an ectopic expression assay and in their in vitro DNA binding properties. Using in vitro selection, we have identified binding sites for EGL-38. However, we show that selected sites function poorly in vivo as EGL-38 response elements, indicating that sequence features in addition to DNA binding determine the efficacy of Pax response elements. The distinction between DNA binding and activity is consistent with the model that other factors commonly play a role in mediating Pax protein target site selection and function in vivo.

Alleles↗
PubMed2004

Evolutionary innovation of the excretory system in Caenorhabditis elegans.

The evolution of complexity relies on changes that result in new gene functions. Here we show that the unique morphological and functional features of the excretory duct cell in C. elegans result from the gain of expression of a single gene. Our results show that innovation can be achieved by altered expression of a transcription factor without coevolution of all target genes.

Animals↗
PubMed2003

Developmental patterning in the Caenorhabditis elegans hindgut.

Developmental pattern formation allows cells within a tissue or organ to coordinate their development and establish cell types in relationship to one another. To better characterize the developmental patterning events within one organ, the C. elegans hindgut, we have analyzed the expression pattern of several genes using green fluorescent protein-based reporter transgenes. In wild-type animals, these genes are expressed in subsets of hindgut cells rather than in individual cell types. In mutant animals, we find that some, but not all, genes expressed in cells with altered development exhibit a corresponding alteration of gene expression. The results are consistent with a model where a combination of factors contribute to each cell's fate, and address how developmental information converges to specify cell types.

Animals↗
PubMed2002

Multiple regulatory changes contribute to the evolution of the Caenorhabditis lin-48 ovo gene.

Recent work points to the importance of changes in gene expression patterns in species-specific differences. Here, we investigate the evolution of the nematode lin-48 ovo gene. lin-48 is expressed in several cells in both Caenorhabditis elegans and Caenorhabditis briggsae, but acts in the excretory duct cell only in C. elegans. We find the differences result both from alterations in the cis-regulatory sequences and in proteins that mediate lin-48 expression. One factor that contributes to the species differences is the bZip protein CES-2. Our results indicate the accumulation of several regulatory changes affecting one gene can contribute to evolutionary change.

Animals↗
PubMedDate not supplied

Evolution of regulatory elements producing a conserved gene expression pattern in Caenorhabditis.

Natural selection acts at the level of function, not at the logistical level of how organisms achieve a particular function. Consequently, significant DNA sequence and regulatory differences can achieve the same function, such as a particular gene expression pattern. To investigate how regulatory features underlying a conserved function can evolve, we compared the regulation of a conserved gene expression pattern in the related species Caenorhabditis elegans and C. briggsae. We find that both C. elegans and C. briggsae express the ovo-related zinc finger gene lin-48 in the same pattern in hindgut cells. However, the regulation of this gene by the Pax-2/5/8 protein EGL-38 differs in two important ways. First, specific differences in the regulatory sequences of lin-48 result in the presence of two redundant EGL-38 response elements in C. elegans, whereas the redundancy is absent in C. briggsae. Second, there is a single egl-38 gene in C. briggsae. In contrast, the gene is duplicated in C. elegans, with only one copy retaining the ability to regulate lin-48 in vivo. These results illustrate molecular changes that can occur despite maintenance of conserved gene function in different species.

Amino Acid Sequence↗