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Regulation of gene expression

About: Regulation of gene expression is a research topic. Over the lifetime, 85456 publications have been published within this topic receiving 5832845 citations. The topic is also known as: GO:0010468 & gene expression regulation.


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Journal ArticleDOI
TL;DR: Administration of an HDAC inhibitor (HDACi) in vivo increased Foxp3 gene expression, as well as the production and suppressive function of regulatory T cells (Treg cells), and HDAC9 proved particularly important in regulatingFoxp3-dependent suppression.
Abstract: Histone/protein deacetylases (HDACs) regulate chromatin remodeling and gene expression as well as the functions of more than 50 transcription factors and nonhistone proteins. We found that administration of an HDAC inhibitor (HDACi) in vivo increased Foxp3 gene expression, as well as the production and suppressive function of regulatory T cells (Treg cells). Although Treg cells express multiple HDACs, HDAC9 proved particularly important in regulating Foxp3-dependent suppression. Optimal Treg function required acetylation of several lysines in the forkhead domain of Foxp3, and Foxp3 acetylation enhanced binding of Foxp3 to the Il2 promoter and suppressed endogenous IL-2 production. HDACi therapy in vivo enhanced Treg-mediated suppression of homeostatic proliferation, decreased inflammatory bowel disease through Treg-dependent effects, and, in conjunction with a short course of low-dose rapamycin, induced permanent, Treg-dependent cardiac and islet allograft survival and donor-specific allograft tolerance. Our data show that use of HDACi allows the beneficial pharmacologic enhancement of both the numbers and suppressive function of Foxp3 + Treg cells. Eukaryotic DNA wound around histone octamers forms nucleosomes that are themselves folded into higher-ordered chromatin structures 1 . Core histones have N-terminal tails extending from compact nucleosomal cores that affect histone interaction and gene regulation. Histone acetyltransferases (HAT) acetylate, and histone/protein deacetylases (HDAC) deacetylate, e-acetyllysine residues of these histone tails. HATs generally increase accessibility and promote gene transcription, whereas HDACs typically dampen histone-DNA and histone– nonhistone protein interactions 2,3 , though exceptions occur 4–6 .H ATs and HDACs also regulate the functions of nonhistone proteins 7 ,a s first described for p53 (ref. 8). An HDACi occupies HDAC catalytic sites, blocking substrate access and causing increased histone acetylation and gene transcription. Although HDACis are under intensive study as anticancer therapies 2 , they also have antiinflammatory effects 9 .H ere we show that HDACi administration increases Foxp3 expression as well as the numbers and function of Foxp3-dependent Treg cells, providing a means to pharmacologically enhance the suppressive properties of Treg cells in vitro and in vivo. RESULTS HDACi use boosts thymic production of natural Foxp3 + Treg cells Treatment of mice with an HDACi, trichostatin-A (TSA) 10 ,i ncreased the proportions and absolute numbers of Foxp3 + CD4 + T cells in

843 citations

Journal ArticleDOI
TL;DR: It is demonstrated that a transcriptional network consisting of S ND1 and its downstream targets is involved in regulating secondary wall biosynthesis in fibers and that NST1, NST2, VND6, and VND7 are functional homologs of SND1 that regulate the same downstream targets in different cell types.
Abstract: SECONDARY WALL-ASSOCIATED NAC DOMAIN PROTEIN1 (SND1) is a master transcriptional switch activating the developmental program of secondary wall biosynthesis. Here, we demonstrate that a battery of SND1-regulated transcription factors is required for normal secondary wall biosynthesis in Arabidopsis thaliana. The expression of 11 SND1-regulated transcription factors, namely, SND2, SND3, MYB103, MYB85, MYB52, MYB54, MYB69, MYB42, MYB43, MYB20, and KNAT7 (a Knotted1-like homeodomain protein), was developmentally associated with cells undergoing secondary wall thickening. Of these, dominant repression of SND2, SND3, MYB103, MYB85, MYB52, MYB54, and KNAT7 significantly reduced secondary wall thickening in fiber cells. Overexpression of SND2, SND3, and MYB103 increased secondary wall thickening in fibers, and overexpression of MYB85 led to ectopic deposition of lignin in epidermal and cortical cells in stems. Furthermore, SND2, SND3, MYB103, MYB85, MYB52, and MYB54 were able to induce secondary wall biosynthetic genes. Direct target analysis using the estrogen-inducible system revealed that MYB46, SND3, MYB103, and KNAT7 were direct targets of SND1 and also of its close homologs, NST1, NST2, and vessel-specific VND6 and VND7. Together, these results demonstrate that a transcriptional network consisting of SND1 and its downstream targets is involved in regulating secondary wall biosynthesis in fibers and that NST1, NST2, VND6, and VND7 are functional homologs of SND1 that regulate the same downstream targets in different cell types.

841 citations

Journal ArticleDOI
TL;DR: These studies have not only highlighted the basic understanding of host–parasite interactions, but also provide key insights into the diversity, regulation and evolution of RNA-silencing pathways.
Abstract: In eukaryotes, small RNA molecules engage in sequence-specific interactions to inhibit gene expression by RNA silencing. This process fulfils fundamental regulatory roles, as well as antiviral functions, through the activities of microRNAs and small interfering RNAs. As a counter-defence mechanism, viruses have evolved various anti-silencing strategies that are being progressively unravelled. These studies have not only highlighted our basic understanding of host-parasite interactions, but also provide key insights into the diversity, regulation and evolution of RNA-silencing pathways.

841 citations

Journal ArticleDOI
TL;DR: Methylation of cytidine nucleotides in GSTP1 regulatory sequences constitutes the most common genomic alteration yet described for human prostate cancer.
Abstract: Hypermethylation of regulatory sequences at the locus of the pi-class glutathione S-transferase gene GSTP1 was detected in 20 of 20 human prostatic carcinoma tissue specimens studied but not in normal tissues or prostatic tissues exhibiting benign hyperplasia. In addition, a striking decrease in GSTP1 expression was found to accompany human prostatic carcinogenesis. Immunohistochemical staining with anti-GSTP1 antibodies failed to detect the enzyme in 88 of 91 prostatic carcinomas analyzed. In vitro, GSTP1 expression was limited to human prostatic cancer cell lines containing GSTP1 alleles with hypomethylated promoter sequences; a human prostatic cancer cell line containing only hypermethylated GSTP1 promoter sequences did not express GSTP1 mRNA or polypeptides. Methylation of cytidine nucleotides in GSTP1 regulatory sequences constitutes the most common genomic alteration yet described for human prostate cancer.

840 citations

Journal ArticleDOI
TL;DR: A cascade of gene activation from maternal RNA/protein sets to zygotic genome activation and thence to MGA gene sets is proposed, which is a first step toward analysis of the complex gene regulatory networks.

839 citations


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Performance
Metrics
No. of papers in the topic in previous years
YearPapers
2023194
2022520
20211,835
20202,294
20192,807
20182,945