DnaA regulates stationary phase-specific expression of an AAA family gene in Caulobacter crescentus.

IBD Genetics: Focus on (Dys) Regulation in Immune Cells and the Epithelium

Dynamic Spatial Regulation in the Bacterial Cell

Chromatin Dynamics and Gene Positioning

Trophoblast cell lineage is established through the first cellular differentiation in mammalian embryogenesis, and its developmental potential is restricted to the extraembryonic tissues contributing solely to the placenta. Several lines of evidence suggest a relative lack of importance of DNA methylation in gene regulation in the extraembryonic tissues when compared with embryonic ones. Here we analyzed the dynamics of epigenetic status in the upstream region of mouse Ddah2 gene, which was found to be specifically repressed in a stem cell population of trophoblast cell lineage. We found a tissue-dependent differentially methylated region in the regulatory region of the Ddah2 gene. This region was hypermethylated in trophoblast stem cells and was hypomethylated in differentiated cells both in vivo and in vitro. This change was well correlated with Ddah2 expression. In addition, in vitro methylation confined to the differentially methylated region was sufficient to repress promoter activity in the reporter assay. Furthermore, a repressive pattern of histone modifications was formed around the differentially methylated region in undifferentiated trophoblast stem cells with repressed Ddah2. Our data suggest that DNA methylation-mediated chromatin remodeling is involved in the regulation of the Ddah2 gene expression and thus is important even in trophoblast cell lineage.

Identification and analysis of Clp protease substrates in "C. crescentus"

141st ENMC International Workshop Inaugural Meeting of the EURO-Laminopathies Project Nuclear Envelope-linked Rare Human Diseases: From Molecular Pathophysiology towards Clinical Applications 10–12 March 2006, Naarden, The Netherlands

RONIN Is an Essential Transcriptional Regulator of Genes Required for Mitochondrial Function in the Developing Retina.

Design Principles for Regulator Gene Expression in a Repressible Gene Circuit

Dominant and Redundant Functions of TFIID Involved in the Regulation of Hepatic Genes

Introduction: Dishevelled (DVL) is a crucial component of Wnt-signaling and is vital for other physiological processes. There are three DVL paralogs, yet the paralog-specific functions and their regulation remain poorly understood. One of the goals of our study is to define how DVL1 mediates Wnt-signaling specificity and how it regulates the transcription of genes that impact tumor-intrinsic modulation of immune cell recruitment. While several studies suggest that DVL proteins could serve as critical mediators of malignancy for breast cancer and other cancer types, the mechanism by which DVL contributes to breast tumor progression and tumor immunology remain unanswered. This study utilizes data from our recent DVL ChIP-seq and RNA-seq analyses, publicly available data, genomic analyses, and other bioinformatics tools to investigate novel mechanisms of how DVL coordinates downstream signaling. Our study seeks to define the elusive function of nuclear DVL with respect to epigenetic and transcriptional regulation in models of triple-negative breast cancer. Methods: DVL ChIP-sequenced reads were aligned against GRCh38.p14, and peaks visualized using an integrative genomic viewer. RNA-seq FASTQ files were trimmed and aligned to GRCh38.p14; read counts were analyzed with edgeR and resulting differentially expressed genes with R and Cytoscape. To determine possible DVL binding partners, transcription factor and protein-protein interaction database mining and subsequent co-immunoprecipitation were performed. Results: Although much remains unknown regarding DVL function and regulation, the discovery of its translocation to the nucleus, binding to novel genomic loci, and regulation of novel gene expression raised new functionality. Our analysis shows DVL binding to core-promoter elements in essential immunological regulatory genes such as STAT1, IFN-y, HLA (-A, B, C, Ds, E, F), and interleukins. Data mining and co-immunoprecipitation analysis have identified several possible nuclear DVL binding partners, including candidate transcription factors that partner with DVL genes to regulate immune cell responses in the tumor microenvironment. DVL KO and WT transcriptional regulation analysis also identified several differentially expressed immunological genes. Summary: We have not only identified DVL binding to the promoter of genes involved in tumorigenesis and immune function but also identified possible DVL binding partners that aid in the regulation of these genes. These findings and future in silico and in vivo approaches will further define a novel DVL regulatory role of tumor and immune signaling in triple-negative breast cancer. Citation Format: Dalia Martinez-Marin, Jenna C van Wunnik, Monica Sharma, Kevin Pruitt. Role of DVL in transcription and epigenetic regulation of immunoregulatory genes in triple-negative breast cancer [abstract]. In: Proceedings of the AACR Special Conference: Tumor Immunology and Immunotherapy; 2022 Oct 21-24; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2022;10(12 Suppl):Abstract nr B03.

Chromatin Remodeling Is a Key Mechanism Underlying Cocaine-Induced Plasticity in Striatum

The Hormonal Control of Gene Transcription

Chk1 is a conserved kinase that imposes cell cycle delays in response to impediments to DNA replication. Recent experiments have further defined effects of Chk1 on the activity of mammalian origins of DNA replication and progression of replication forks. Moreover, Chk1 now appears to help defend genomic integrity through effects on several other pathways, including Fanconi anemia proteins, the mitotic spindle, and transcription of cell cycle-related genes. These findings can account for the requirement for Chk1 in normal proliferating cells of the early embryo and suggest the potential for diverse effects of Chk1 inhibition in cancer therapy.

Regulation of chromosomal replication in Caulobacter crescentus

Human immunodeficiency virus type 1 (HIV-1) infections have different patterns of expression in different T-cell lines. HIV-1 encodes regulatory as well as structural genes. The role of HIV-1 regulatory gene expression in determining different patterns of infection was explored in four T-cell lines: C8166, H9, A3.01, and Jurkat. The hypothesis being tested was that differences in the expression of regulatory genes would determine differences in the kinetics of infection. To study patterns of regulatory and structural gene expression, RNA was isolated from cultures infected with HIV-1-NL4-3 (NL4-3). During the early and acute phases of infection, the absolute amounts of viral RNA differed in the four T-cell lines. However, the relative proportions of messages for regulatory and structural genes were similar. Thus, differences in the kinetics of infection in C8166, H9, A3.01 and Jurkat cells were not determined by differences in the relative levels of expression of regulatory and structural genes. Analyses of RNA samples from the chronic phase of infection revealed the consistent appearance of novel RNase sensitive sites in H9 and Jurkat cultures. These marked the emergence of viral variants with high ability to establish chronic virus producers. These variants were specifically selected in the chronic phase since they did not undergo selection during serial passage of the virus through the lytic phase of infection. Sequence analysis of the region with the novel RNase sensitive sites revealed the co-mapping of nucleotide changes with each of the novel sites. Most of these differences represented a sense mutation in tat and the abrogation of the initiator methionine of vpu . However, the selected mutations in tat and vpu were not sufficient, by themselves, to affect the ability of NL4-3 to establish chronic virus producers (Chapters I and II). Further studies on the roles of viral sequences in the chronic phase of infection were undertaken using constructed viruses. Two molecularly cloned viruses, NL4-3 and HIV-1-HXB-2 (HXB-2), were used as parents. NL4-3 has a low ability to establish chronic virus producers. In contrast, HXB-2 has a high ability to establish chronic virus producers. NL4-3 encodes all known HIV-1 genes, whereas HXB-2 is defective for three auxiliary genes: vpr, vpu, and nef . In addition, both viruses differ at other positions throughout the genome. The first series of constructed viruses tested whether differences in auxiliary gene expression determined differences in the ability of NL4-3 and HXB-2 to establish chronic virus producers. NL4-3 mutants containing all possible combinations of the three defective genes in HXB-2 were constructed. Analysis of the ability of these mutants to establish chronic virus producers revealed that vpr and nef limit the ability of NL4-3 to establish chronic virus producers. This was shown by viruses with defects in both of these genes having high ability to establish chronic…