Association of a change in chromatin structure with a tissue-specific switch in transcription start sites in the α2(I) collagen gene

ABSTRACTCharacterizing transcription start sites is essential for understanding the regulatory mechanisms that control gene expression. Recently, a new bovine genome assembly (ARS-UCD1.2) with high continuity, accuracy, and completeness was released; however, the functional annotation of the bovine genome lacks precise transcription start sites and includes a low number of transcripts in comparison to human and mouse. Using the RAMPAGE approach, this study identified transcription start sites at high resolution in a large collection of bovine tissues. We found several known and novel transcription start sites attributed to promoters of protein coding and lncRNA genes that were validated through experimental and in silico evidence. With these findings, the annotation of transcription start sites in cattle reached a level comparable to the mouse and human genome annotations. In addition, we identified and characterized transcription start sites for antisense transcripts derived from bidirectional promoters, potential lncRNAs, mRNAs, and pre-miRNAs. We also analyzed the quantitative aspects of RAMPAGE data for producing a promoter activity atlas, reaching highly reproducible results comparable to traditional RNA-Seq. Lastly, gene co-expression networks revealed an impressive use of tissue-specific promoters, especially between brain and testicle, which expressed several genes in common from alternate transcription start sites. Regions surrounding co-expressed modules were enriched in binding factor motifs representative of their tissues. This annotation will be highly useful for future studies on expression control in cattle and other species. Furthermore, these data provide significant insight into transcriptional activity for a comprehensive set of tissues.

Download Full-text

Comprehensive nucleosome mapping of the human genome in cancer progression

10.1101/021618 ◽

2015 ◽

Author(s):

Brooke Druliner ◽

Daniel Vera ◽

Ruth Johnson ◽

Xiaoyang Ruan ◽

Lynne Apone ◽

...

Keyword(s):

Cancer Progression ◽

Chromatin Structure ◽

Colon Adenocarcinoma ◽

Transcription Start ◽

Transcription Start Sites ◽

Genome Wide ◽

Early Adenocarcinoma ◽

Capture Method ◽

Nucleosome Mapping

Altered chromatin structure is a hallmark of cancer, and inappropriate regulation of chromatin structure may represent the origin of transformation. Important studies have mapped human nucleosome distributions genome wide, but the role of chromatin structure in cancer progression has not been addressed. We developed a MNase-Transcription Start Site Sequence Capture method (mTSS-seq) to map the nucleosome distribution at human transcription start sites genome-wide in primary human lung and colon adenocarcinoma tissue. Here, we confirm that nucleosome redistribution is an early, widespread event in lung (LAC) and colon (CRC) adenocarcinoma. These altered nucleosome architectures are consistent between LAC and CRC patient samples indicating that they may serve as important early adenocarcinoma markers. We demonstrate that the nucleosome alterations are driven by the underlying DNA sequence and potentiate transcription factor binding. We conclude that DNA-directed nucleosome redistributions are widespread early in cancer progression. We have proposed an entirely new hierarchical model for chromatin-mediated genome regulation.

Download Full-text

Tissue-specific usage of transposable element-derived promoters in mouse development

Genome Biology ◽

10.1186/s13059-020-02164-3 ◽

2020 ◽

Vol 21 (1) ◽

Author(s):

Benpeng Miao ◽

Shuhua Fu ◽

Cheng Lyu ◽

Paul Gontarz ◽

Ting Wang ◽

...

Keyword(s):

Expression Patterns ◽

Early Embryo ◽

Mouse Tissue ◽

Open Chromatin ◽

Mouse Development ◽

Transcription Start ◽

Specific Expression ◽

Tissue Specific ◽

Transcription Start Sites ◽

Tissue Specific Expression

Abstract Background Transposable elements (TEs) are a significant component of eukaryotic genomes and play essential roles in genome evolution. Mounting evidence indicates that TEs are highly transcribed in early embryo development and contribute to distinct biological functions and tissue morphology. Results We examine the epigenetic dynamics of mouse TEs during the development of five tissues: intestine, liver, lung, stomach, and kidney. We found that TEs are associated with over 20% of open chromatin regions during development. Close to half of these accessible TEs are only activated in a single tissue and a specific developmental stage. Most accessible TEs are rodent-specific. Across these five tissues, 453 accessible TEs are found to create the transcription start sites of downstream genes in mouse, including 117 protein-coding genes and 144 lincRNA genes, 93.7% of which are mouse-specific. Species-specific TE-derived transcription start sites are found to drive the expression of tissue-specific genes and change their tissue-specific expression patterns during evolution. Conclusion Our results suggest that TE insertions increase the regulatory potential of the genome, and some TEs have been domesticated to become a crucial component of gene and regulate tissue-specific expression during mouse tissue development.

Download Full-text

DBTSS provides a tissue specific dynamic view of Transcription Start Sites

Nucleic Acids Research ◽

10.1093/nar/gkp1017 ◽

2009 ◽

Vol 38 (suppl_1) ◽

pp. D98-D104 ◽

Cited By ~ 41

Author(s):

Riu Yamashita ◽

Hiroyuki Wakaguri ◽

Sumio Sugano ◽

Yutaka Suzuki ◽

Kenta Nakai

Keyword(s):

Transcription Start ◽

Tissue Specific ◽

Transcription Start Sites ◽

Dynamic View

Download Full-text

Accurate transcription start sites enable mining for the cis-regulatory determinants of tissue specific gene expression

10.1101/2020.09.01.278424 ◽

2020 ◽

Author(s):

Mitra Ansariola ◽

Valerie N. Fraser ◽

Sergei A. Filichkin ◽

Maria G. Ivanchenko ◽

Zachary A. Bright ◽

...

Keyword(s):

Gene Expression ◽

Binding Sites ◽

Chromatin Accessibility ◽

Specific Gene ◽

Open Chromatin ◽

Transcription Start ◽

Tissue Specific ◽

Transcription Start Sites ◽

Tissue Specific Gene ◽

Specific Gene Expression

AbstractAcross tissues, gene expression is regulated by a combination of determinants, including the binding of transcription factors (TFs), along with other aspects of cellular state. Recent studies emphasize the importance of both genetic and epigenetic states – TF binding sites and binding site chromatin accessibility have emerged as potentially causal determinants of tissue specificity. To investigate the relative contributions of these determinants, we constructed three genome-scale datasets for both root and shoot tissues of the same Arabidopsis thaliana plants: TSS-seq data to identify Transcription Start Sites, OC-seq data to identify regions of Open Chromatin, and RNA-seq data to assess gene expression levels. For genes that are differentially expressed between root and shoot, we constructed a machine learning model predicting tissue of expression from chromatin accessibility and TF binding information upstream of TSS locations. The resulting model was highly accurate (over 90% auROC and auPRC), and our analysis of model contributions (feature weights) strongly suggests that patterns of TF binding sites within ∼500 nt TSS-proximal regions are predominant explainers of tissue of expression in most cases. Thus, in plants, cis-regulatory control of tissue-specific gene expression appears to be primarily determined by TSS-proximal sequences, and rarely by distal enhancer-like accessible chromatin regions. This study highlights the exciting future possibility of a native TF site-based design process for the tissue-specific targeting of plant gene promoters.

Download Full-text

Alternative promoters and cardiac muscle cell-specific expression of the Na+/Ca2+exchanger gene

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1998.274.1.h217 ◽

1998 ◽

Vol 274 (1) ◽

pp. H217-H232 ◽

Cited By ~ 9

Author(s):

Susanne B. Nicholas ◽

Weidong Yang ◽

Shwu-Luan Lee ◽

Hong Zhu ◽

Kenneth D. Philipson ◽

...

Keyword(s):

Binding Sites ◽

Alternative Promoters ◽

Limited Data ◽

Transcription Start ◽

Specific Expression ◽

Tissue Specific ◽

Transcription Start Sites ◽

Gata Factors ◽

Specific Alternative ◽

Specific Factors

Many studies have investigated the regulation of the Na+/Ca2+exchanger, NCX1, but limited data exist on transcriptional regulation of the NCX1 gene. We have identified the transcription start sites of three tissue-specific alternative promoters of NCX1 transcripts from rat heart, kidney, and brain. We have characterized the cardiac NCX1 promoter, from which the most abundant quantities of NCX1 transcripts are expressed. Transfection of primary cardiac myocytes, CHO cells, and COS-7 cells with overlapping genomic DNA fragments spanning the NCX1 cardiac transcription start site has uncovered a cardiac cell-specific minimum promoter from −137 to +85. The cardiac NCX1 promoter is TATA-less but has putative binding sites for cardiac-specific GATA factors, an E box, and an Inr as well as multiple active enhancers. The kidney NCX1 promoter has a typical TATA box and binding sites for several tissue-specific factors. The brain NCX1 promoter is very GC-rich and possesses several Sp-1 binding sites consistent with its ubiquitous expression.

Download Full-text

28 The functional annotation of the sheep genome project

Journal of Animal Science ◽

10.1093/jas/skz122.029 ◽

2019 ◽

Vol 97 (Supplement_2) ◽

pp. 16-16 ◽

Cited By ~ 1

Author(s):

Brenda M Murdoch

Keyword(s):

Gene Expression ◽

Functional Annotation ◽

Specific Gene ◽

Biological Traits ◽

Transcription Start ◽

Detailed Understanding ◽

Tissue Specific ◽

Transcription Start Sites ◽

Chip Sequencing ◽

Tissue Specific Gene

Abstract Reference genomes for some agricultural animals have been available for almost a decade; however, the annotation of these genomes remain an ongoing process. As a result, a detailed understanding of gene and gene product regulation that impart biological traits and physiological systems remains elusive. Through the Functional Annotation of ANimal Genomes (FAANG) consortium, coordinated efforts of the international scientific community are addressing this deficiency. The overarching goal of the Ovine FAANG project is to generate comprehensive transcriptome and chromatin state data sets from a large variety of adult tissues to accurately map functional elements of the ovine genome. In total, 100 tissues were collected (snap & slow frozen) from Benz 2616, the new reference genome, Oar_rambouillet_v1.0. Three methods of RNA sequencing have been utilized to fully understand tissue specific gene expression profiles. Transcript sequencing using poly-A+ messenger RNA has been completed for 60 tissues, whereas small microRNA as well as long read Iso-Sequencing data have been generated in a subset of these tissues. To further complement the gene expression data and to identify active promoters and confirm transcription start sites, Cap Analysis of Gene Expression (CAGE) has been completed. Histone modifications are being examined through Chromatin Immuno-precipitation (ChIP) sequencing to define different regulatory features. We are capitalizing on the knowledge that H3K4me3 and H3K27ac are enriched at transcription start sites and H3K4me1 at enhancer sites of actively transcribed genes, whereas H3K27me3 represses gene transcription. To determine chromatin accessibility, ATAC-seq is being performed for the 60 highest priority tissues. DNA methylation assays, specifically whole genome bisulfite and reduced representation bisulfite sequencing, are being performed on these tissues. This project will provide the first detailed understanding of tissue-specific gene regulatory signals and gene products, imparting a greater understanding of the mechanisms for genome to functional phenotype variation within sheep.

Download Full-text