Intronic enhancers regulate the expression of genes involved in tissue-specific functions and homeostasis

AbstractTissue function and homeostasis reflect the gene expression signature by which the combination of ubiquitous and tissue-specific genes contribute to the tissue maintenance and stimuli-responsive function. Enhancers are central to control this tissue-specific gene expression pattern. Here, we explore the correlation between the genomic location of enhancers and their role in tissue-specific gene expression. We found that enhancers showing tissue-specific activity are highly enriched in intronic regions and regulate the expression of genes involved in tissue-specific functions, while housekeeping genes are more often controlled by intergenic enhancers. Notably, an intergenic-to-intronic active enhancers continuum is observed in the transition from developmental to adult stages: the most differentiated tissues present higher rates of intronic enhancers, while the lowest rates are observed in embryonic stem cells. Altogether, our results suggest that the genomic location of active enhancers is key for the tissue-specific control of gene expression.

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Tissue-specific Gene Expression Prediction Associates Vitiligo with SUOX through an Active Enhancer

10.1101/337196 ◽

2018 ◽

Cited By ~ 2

Author(s):

Zhihua Qi ◽

Shiqi Xie ◽

Rui Chen ◽

Haji A. Aisa ◽

Gary C. Hon ◽

...

Keyword(s):

Gene Expression ◽

T Cell Activation ◽

Cell Activation ◽

Gene Expression Pattern ◽

Specific Gene ◽

Gene Expressions ◽

Tissue Specific ◽

Tissue Specific Gene ◽

Specific Gene Expression ◽

Putative Enhancer

Vitiligo is an autoimmune disease featuring destruction of melanocytes, which results in patchy depigemtation of skin and hair; two vitiligo GWAS studies identified multiple significant associations, including SNPs in 12q13.2 region. But one study ascribed the association to IKZF4 because it encodes a regulator of T cell activation and is associated with two autoimmune diseases; while the other study ascribed the association to PMEL because it encodes melanocyte protein and has the strongest differential expression between vitiligo lesions and perilesional normal skins. Here we show that vitiligo associated gene in 12q13.2 region is SUOX. Reanalyzing one GWAS dataset, we predicted tissue-specific gene-expression by leveraging Genotype-Tissue Expression (GTEx) datasets, and performed association mapping between the predicted gene-expressions and vitiligo status. SUOX expression is significantly associated with vitiligo in both Nerve (tibia) and Skin (sun exposed) tissues. Epigenetic marks encompass the most significant eQTL of SUOX in both nerve and skin tissues suggest a putative enhancer 3Kb downstream of SUOX. We silenced the putative enhancer using the CRISPR interference system and observed 50% decrease in SUOX expression in K562 cells, a cell line that has similar DNase hypersensitive sites and gene expression pattern to the skin tissue at SUOX locus. Our work provided an example to make sense GWAS hits through examining factors that affect gene expression both computationally and experimentally.

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Histones: genetic diversity and tissue-specific gene expression

Histochemistry and Cell Biology ◽

10.1007/s004180050083 ◽

1997 ◽

Vol 107 (1) ◽

pp. 1-10 ◽

Cited By ~ 68

Author(s):

D. Doenecke ◽

W. Albig ◽

C. Bode ◽

B. Drabent ◽

K. Franke ◽

...

Keyword(s):

Gene Expression ◽

Genetic Diversity ◽

Specific Gene ◽

Tissue Specific ◽

Tissue Specific Gene ◽

Specific Gene Expression

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Food Shortage Causes Differential Effects on Body Composition and Tissue-Specific Gene Expression in Salmon Modified for Increased Growth Hormone Production

Marine Biotechnology ◽

10.1007/s10126-015-9654-8 ◽

2015 ◽

Vol 17 (6) ◽

pp. 753-767 ◽

Cited By ~ 5

Author(s):

Jason Abernathy ◽

Stéphane Panserat ◽

Thomas Welker ◽

Elisabeth Plagne-Juan ◽

Dionne Sakhrani ◽

...

Keyword(s):

Gene Expression ◽

Growth Hormone ◽

Body Composition ◽

Food Shortage ◽

Specific Gene ◽

Hormone Production ◽

Tissue Specific ◽

Differential Effects ◽

Tissue Specific Gene ◽

Specific Gene Expression

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Blood—Brain Barrier Genomics

Journal of Cerebral Blood Flow & Metabolism ◽

10.1097/00004647-200101000-00008 ◽

2001 ◽

Vol 21 (1) ◽

pp. 61-68 ◽

Cited By ~ 105

Author(s):

Jian Yi Li ◽

Ruben J. Boado ◽

William M. Pardridge

Keyword(s):

Gene Expression ◽

Blood Brain Barrier ◽

Brain Barrier ◽

Specific Gene ◽

Microvascular Endothelium ◽

Tissue Specific ◽

Tissue Specific Gene ◽

Specific Gene Expression ◽

Blood Brain ◽

Tester Cdna

The blood–brain barrier (BBB) is formed by the brain microvascular endothelium, and the unique transport properties of the BBB are derived from tissue-specific gene expression within this cell. The current studies developed a gene microarray approach specific for the BBB by purifying the initial mRNA from isolated rat brain capillaries to generate tester cDNA. A polymerase chain reaction–based subtraction cloning method, suppression subtractive hybridization (SSH), was used, and the BBB cDNA was subtracted with driver cDNA produced from mRNA isolated from rat liver and kidney. Screening 5% of the subtracted tester cDNA resulted in identification of 50 gene products and more than 80% of those were selectively expressed at the BBB; these included novel gene sequences not found in existing databases, ESTs, and known genes that were not known to be selectively expressed at the BBB. Genes in the latter category include tissue plasminogen activator, insulin-like growth factor-2, PC-3 gene product, myelin basic protein, regulator of G protein signaling 5, utrophin, IκB, connexin-45, the class I major histocompatibility complex, the rat homologue of the transcription factors hbrm or EZH1, and organic anion transporting polypeptide type 2. Knowledge of tissue-specific gene expression at the BBB could lead to new targets for brain drug delivery and could elucidate mechanisms of brain pathology at the microvascular level.

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