A Global Vista of the Epigenomic State of the Mouse Submandibular Gland

2021 ◽  
pp. 002203452110120
Author(s):  
C. Gluck ◽  
S. Min ◽  
A. Oyelakin ◽  
M. Che ◽  
E. Horeth ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcriptional Control ◽  
Expression Patterns ◽  
Global Gene Expression ◽  
Regulatory Elements ◽  
Specific Gene ◽  
Submandibular Salivary Gland ◽  
Data Sets ◽  
Control Mechanisms ◽  
Chromatin Immunoprecipitation Sequencing

The parotid, submandibular, and sublingual glands represent a trio of oral secretory glands whose primary function is to produce saliva, facilitate digestion of food, provide protection against microbes, and maintain oral health. While recent studies have begun to shed light on the global gene expression patterns and profiles of salivary glands, particularly those of mice, relatively little is known about the location and identity of transcriptional control elements. Here we have established the epigenomic landscape of the mouse submandibular salivary gland (SMG) by performing chromatin immunoprecipitation sequencing experiments for 4 key histone marks. Our analysis of the comprehensive SMG data sets and comparisons with those from other adult organs have identified critical enhancers and super-enhancers of the mouse SMG. By further integrating these findings with complementary RNA-sequencing based gene expression data, we have unearthed a number of molecular regulators such as members of the Fox family of transcription factors that are enriched and likely to be functionally relevant for SMG biology. Overall, our studies provide a powerful atlas of cis-regulatory elements that can be leveraged for better understanding the transcriptional control mechanisms of the mouse SMG, discovery of novel genetic switches, and modulating tissue-specific gene expression in a targeted fashion.

scholarly journals Beyond the ENCODE project: using genomics and epigenomics strategies to study enhancer evolution

2013 ◽  
Vol 368 (1632) ◽  
pp. 20130022 ◽  
Author(s):  
Noboru Jo Sakabe ◽  
Marcelo A. Nobrega
Keyword(s):  
Gene Expression ◽  
Target Genes ◽  
Expression Patterns ◽  
Dna Interaction ◽  
Regulatory Elements ◽  
Specific Gene ◽  
Genome Wide ◽  
Identify Transcription Factor ◽  
Specific Proteins ◽  
Species Specific

The complex expression patterns observed for many genes are often regulated by distal transcription enhancers. Changes in the nucleotide sequences of enhancers may therefore lead to changes in gene expression, representing a central mechanism by which organisms evolve. With the development of the experimental technique of chromatin immunoprecipitation (ChIP), in which discrete regions of the genome bound by specific proteins can be identified, it is now possible to identify transcription factor binding events (putative cis -regulatory elements) in entire genomes. Comparing protein–DNA binding maps allows us, for the first time, to attempt to identify regulatory differences and infer global patterns of change in gene expression across species. Here, we review studies that used genome-wide ChIP to study the evolution of enhancers. The trend is one of high divergence of cis -regulatory elements between species, possibly compensated by extensive creation and loss of regulatory elements and rewiring of their target genes. We speculate on the meaning of the differences observed and discuss that although ChIP experiments identify the biochemical event of protein–DNA interaction, it cannot determine whether the event results in a biological function, and therefore more studies are required to establish the effect of divergence of binding events on species-specific gene expression.

scholarly journals Global Analysis of Cell Type-Specific Gene Expression

2003 ◽  
Vol 4 (2) ◽  
pp. 208-215 ◽  
Author(s):  
David W. Galbraith
Keyword(s):  
Gene Expression ◽  
Fluorescent Protein ◽  
Global Analysis ◽  
Expression Patterns ◽  
Three Dimensional ◽  
Global Gene Expression ◽  
Cell Types ◽  
Reasonable Assumption ◽  
Specific Gene ◽  
Different Cell Types

The tissues and organs of multicellular eukaryotes are frequently observed to comprise complex three-dimensional interspersions of different cell types. It is a reasonable assumption that different global patterns of gene expression are found within these different cell types. This review outlines general experimental strategies designed to characterize these global gene expression patterns, based on a combination of methods of transgenic fluorescent protein (FP) expression and targeting, of flow cytometry and sorting and of high-throughput gene expression analysis.

BCL6 Transcriptionally Reprograms the DLBCL Genome by Forming Distinct Biochemically Active Complexes on Genes Corresponding to Different Pathways.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2646-2646
Author(s):  
Jose M. Polo ◽  
Katerina Chatzi ◽  
Tania Dell’Oso ◽  
Paola Lev ◽  
Ari Melnick
Keyword(s):  
Gene Expression ◽  
Cell Death ◽  
Chromatin Structure ◽  
Transcriptional Control ◽  
Target Genes ◽  
Biological Effects ◽  
Hematologic Malignancies ◽  
Specific Gene ◽  
Control Mechanisms ◽  
Biochemical Mechanisms

Abstract Aberrant gene expression is a hallmark of cancer, and so it is not surprising that the most common category of oncogenes and tumor suppressors involved in hematologic malignancies are transcription factors. These factors mediate their effects by nucleating biochemically active cofactor complexes to modify the chromatin structure of their respective target genes. BCL6 is a transcriptional repressor and the most commonly involved oncogene in diffuse large B-cell lymphomas. BCL6 represses genes by recruiting several corepressor complexes including SMRT, N-CoR, BCoR; all of which bind to BCL6 through its BTB domain. Each of these complexes has different biochemical functions (e.g. BCoR forms a polycomb complex vs. SMRT which forms an HDAC3 complex). Moreover, our preliminary data suggested that BCL6 uses different sets of corepressors to mediate distinct biological effects, possibly by using different biochemical mechanisms at specific sets of target genes. Therefore, we hypothesized that BCL6 regulates its target genes using different biochemical tools, allowing it to exquisitely fine tune gene expression and provide specific control mechanisms for different biological functions. In order to test this hypothesis we first identified the direct target genes of BCL6 SMRT, N-CoR and BCoR by ChIP-on-chip in DLBCL cells (Ly1 cells) in multiple replicates, and examined whether the overlapping sets of genes corresponded to different gene pathways. We used a 24,000 promoter microarray representing 1.5 KB of sequence for each gene. The results show reproducible binding of BCL6 at 940 promoters, While BCoR bound to 770, SMRT to 545 and N-CoR to 487 promoters respectively. BCL6 and BCoR overlapped at 400 genes, preferentially involved in involve in cell cycle, cell death chromatin structure, ubiquitin dependent process and chemotaxis. BCL6 and SMRT overlapped on 376 genes, involved in immune response, cell motility and also as BCOR cell death, while N-CoR and BCL6 overlapped on 100 genes including transcriptional control and cell death pathways. The overlap between BCoR and SMRT was at 200 genes, BCoR and N-CoR at 60 genes and SMRT and N-CoR at 85 genes. All three overlapped at 50 genes. We also examined whether these corepressors were associated with specific combinations of histone modifications including H3K9 acetylation, H3K9 methylation, H3K4 methylation, H3K27 methylation, H4K16 acetylation and H3K36 acetylation. Taken together, the data indicate that specific subsets of BCL6 target genes are dependent on distinct biochemical mechanisms, suggesting that additional layers of biochemical complexity govern formation of gene repression complexes in DLBCL cells and providing opportunities for highly specific therapeutic targeting of specific gene programs.

scholarly journals A genome-wide transcriptional analysis of morphology determination inCandida albicans

2013 ◽  
Vol 24 (3) ◽  
pp. 246-260 ◽  
Author(s):  
Patricia L. Carlisle ◽  
David Kadosh
Keyword(s):  
Gene Expression ◽  
Fungal Infections ◽  
Transcriptional Profiling ◽  
Expression Patterns ◽  
Global Gene Expression ◽  
Transcriptional Analysis ◽  
Specific Gene ◽  
Genome Wide ◽  
A Genome ◽  
Genetically Manipulated

Candida albicans, the most common cause of human fungal infections, undergoes a reversible morphological transition from yeast to pseudohyphal and hyphal filaments, which is required for virulence. For many years, the relationship among global gene expression patterns associated with determination of specific C. albicans morphologies has remained obscure. Using a strain that can be genetically manipulated to sequentially transition from yeast to pseudohyphae to hyphae in the absence of complex environmental cues and upstream signaling pathways, we demonstrate by whole-genome transcriptional profiling that genes associated with pseudohyphae represent a subset of those associated with hyphae and are generally expressed at lower levels. Our results also strongly suggest that in addition to dosage, extended duration of filament-specific gene expression is sufficient to drive the C. albicans yeast-pseudohyphal-hyphal transition. Finally, we describe the first transcriptional profile of the C. albicans reverse hyphal-pseudohyphal-yeast transition and demonstrate that this transition involves not only down-regulation of known hyphal-specific, genes but also differential expression of additional genes that have not previously been associated with the forward transition, including many involved in protein synthesis. These findings provide new insight into genome-wide expression patterns important for determining fungal morphology and suggest that in addition to similarities, there are also fundamental differences in global gene expression as pathogenic filamentous fungi undergo forward and reverse morphological transitions.

Gene Regulation: A Genomic Perspective

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. SCI-10-SCI-10
Author(s):  
John Stamatoyannopoulos
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Conflicts Of Interest ◽  
Expression Patterns ◽  
Regulatory Elements ◽  
Gene Expression Patterns ◽  
Specific Gene ◽  
Regulatory Regions ◽  
Regulatory Pathways ◽  
Wide Range

Abstract Regulatory elements control the anatomic and cellular contexts, timing, and magnitude of gene expression patterns. Under the ENCODE and Roadmap Epigenomics Projects, human regulatory DNA has been mapped using a variety of approaches in over 300 cell and tissue types and developmental states. Collectively, the human genome encodes several million regulatory elements, most of which are located at some distance from promoters. The vast majority of these elements exhibit exquisite cell-and lineage-selective activation patterns, providing novel insights into the coordination of gene expression patterns. Genomic footprinting is a new and powerful technology that enables simultaneous profiling of the occupancy of hundreds of sequence-specific transcription factors within regulatory regions. These profiles in turn enable construction of transcription factor regulatory networks that are providing new insights into how cell-and lineage-specific gene expression programs arise. Hundreds of genetic variants associated with a wide range of hematological traits and disorders localize within regulatory regions. Many such variants disrupt specific transcription factor-DNA interactions, exposing pathophysiologically relevant transcriptional regulatory pathways. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Mechanisms of YAP/TAZ transcriptional control

Cell Stress ◽  
2021 ◽  
Vol 5 (11) ◽  
pp. 167-172
Author(s):  
Giusy Battilana ◽  
Francesca Zanconato ◽  
Stefano Piccolo
Keyword(s):  
Gene Expression ◽  
Regulatory Networks ◽  
Transcriptional Control ◽  
Cell Transformation ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Regulatory Elements ◽  
Specific Gene ◽  
Chromatin Regulators ◽  
Small Set

Dysregulated gene expression is intrinsic to cell transformation, tumorigenesis and metastasis. Cancer-specific gene-expression profiles stem from gene regulatory networks fueled by genetic and epigenetic defects, and by abnormal signals of the tumor microenvironment. These oncogenic signals ultimately engage the transcriptional machinery on the cis -regulatory elements of a host of effector genes, through recruitment of transcription factors (TFs), co-activators and chromatin regulators. That said, whether gene -expression in cancer cells is the chaotic product of myriad regulations or rather a relatively ordered process orchestrated by few TFs (master regulators) has long remained enigmatic. Recent work on the YAP/TAZ co-activators has been instrumental to break new ground into this outstanding issue, revealing that tumor cells hijack growth programs that are active during development and regeneration through engagement of a small set of interconnected TFs and their nuclear partners.

scholarly journals Repression precedes the stepwise evolution of a highly specific gene expression pattern

2020 ◽  
Author(s):  
Jian Pu ◽  
Zinan Wang ◽  
Haosu Cong ◽  
Jacqueline S.R. Chin ◽  
Jessa Justen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Expression Pattern ◽  
Expression Patterns ◽  
Gene Expression Pattern ◽  
Regulatory Elements ◽  
Fatty Acyl ◽  
Specific Gene ◽  
Spatial Expression ◽  
Origin And Evolution ◽  
And Function

AbstractWell-controlled gene expression is critical for the proper development and function of many traits. Highly-specific temporal and spatial expression patterns are often due to the overlapping activities of activator and repressor sequences that form cis-regulatory elements called enhancers. While many studies have shown that evolutionary changes in enhancers can result in novel traits, few studies illuminate how enhancers originate, how activator and repressor sequences interact during enhancer evolution, and the order in which they evolve. Here, we traced the evolutionary origin of a recently evolved enhancer that drives the expression of the fatty acyl-CoA elongase, bond, specifically in the semicircular wall epithelium (swe) of the Drosophila male ejaculatory bulb (EB). We show that this enhancer consists of two activator regions that drive bond expression in the entire EB and a repressor region that restricts expression specifically to the EB swe. Interestingly, the repressor region preceded the evolution of the two activator regions. The evolution of the first activator region, consisting of two putative Abdominal-B sites, did not drive expression in the EB due to the action of the repressor region. Expression of bond in the EB swe requires the evolution of the second activator region, which does not drive expression on its own, but synergizes with the first activator region and the repressor region to produce a highly-specific spatial expression pattern. Our results show that the origin and evolution of a novel enhancer require multiple steps and the evolution of repressor sequences can precede the evolution of activator sequences.

Abstract 348: Multi-Species Genome-Wide Analyses of the Specification of Individual Cardiac Cell Fates

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Brian Busser ◽  
Julian Haimovich ◽  
Guokai Chen ◽  
Ivan Ovcharenko ◽  
Alan Michelson
Keyword(s):  
Gene Expression ◽  
Large Scale ◽  
Expression Patterns ◽  
Embryonic Stem ◽  
Regulatory Elements ◽  
Cardiac Cells ◽  
Specific Gene ◽  
Cardiac Cell ◽  
Cell Fates ◽  
Cell Fate Decisions

There are remarkable molecular and embryological similarities in cardiogenesis between Drosophila and vertebrates. Cells comprising the Drosophila heart can be subdivided into individual identities based on differences in morphology, function and gene expression patterns. Recent studies have shown that differential modifications of histone proteins, in vivo transcription factor (TF) binding, and the presence of particular TF binding motifs can be used as predictive signatures of the enhancers that govern cell-specific gene expression. Here we used discriminative training methods within an integrative, multi-species framework to uncover the motifs, enhancers and genes underlying cardiac cell fate decisions. As an initial step, we undertook a large-scale validation of Drosophila heart enhancers, which revealed enhancer activities in distinct subpopulations of cardiac cells. To identify related cell-specific regulatory elements, we used the validated enhancers as a training set in a machine learning approach that integrated TF motifs with ChIP data for both TF binding and histone modifications. Empirical validation of candidate enhancers predicted by this method confirmed activity in the appropriate cardiac cells. By clustering the motifs derived from the individual cardiac classifiers, we identified and validated sequence features which discriminate specific cellular identities. Next, we asked if similar predictive signatures underlie mouse and human cardiomyocyte (CM) differentiation from embryonic stem cells (ESCs). We show that the distribution of histone marks found within differentiating human and mouse ESCs indeed predict genes potentially critical for CM differentiation, with the best predictions provided by the overlapping mouse and human candidates. We evaluated this result in a large-scale RNAi-based screen of Drosophila orthologs of the mammalian genes, which uncovered dozens of novel cardiogenic regulators whose function is being tested in differentiating human ESCs. In total, these results document the utility of computational modeling combined with empirical testing to uncover the enhancers, TF motifs and genes which characterize individual cardiac cell fates in both invertebrate and mammalian species.

scholarly journals Dynamic Interactions of Transcription Factors and Enhancer Reprogramming in Cancer Progression

2021 ◽  
Vol 11 ◽  
Author(s):  
Emily Zboril ◽  
Hannah Yoo ◽  
Lizhen Chen ◽  
Zhijie Liu
Keyword(s):  
Gene Expression ◽  
Cancer Progression ◽  
Expression Patterns ◽  
Therapy Resistance ◽  
Regulatory Elements ◽  
Specific Gene ◽  
Dynamic Interactions ◽  
Genome Wide ◽  
Dna Regulatory Elements

While improved tumor treatment has significantly reduced the overall mortality rates, invasive progression including recurrence, therapy resistance and metastasis contributes to the majority of deaths caused by cancer. Enhancers are essential distal DNA regulatory elements that control temporal- or spatial-specific gene expression patterns during development and other biological processes. Genome-wide sequencing has revealed frequent alterations of enhancers in cancers and reprogramming of distal enhancers has emerged as one of the important features for tumors. In this review, we will discuss tumor progression-associated enhancer dynamics, its transcription factor (TF) drivers and how enhancer reprogramming modulates gene expression during cancer invasive progression. Additionally, we will explore recent advancements in contemporary technology including single-cell sequencing, spatial transcriptomics and CUT&RUN, which have permitted integrated studies of enhancer reprogramming in vivo. Given the essential roles of enhancer dynamics and its drivers in controlling cancer progression and treatment outcome, understanding these changes will be paramount in mitigating invasive events and discovering novel therapeutic targets.

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