Faculty Opinions recommendation of DNA looping induced by a transcriptional enhancer in vivo.

2005 ◽  
Author(s):  
Jim Maher
Keyword(s):  
Dna Looping ◽  
Transcriptional Enhancer

scholarly journals TAF7L modulates brown adipose tissue formation

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Haiying Zhou ◽  
Bo Wan ◽  
Ivan Grubisic ◽  
Tommy Kaplan ◽  
Robert Tjian
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Core Promoter ◽  
Uncoupling Protein ◽  
Dna Looping ◽  
Chromatin Interactions ◽  
Brown Adipose ◽  
Important Regulator

Brown adipose tissue (BAT) plays an essential role in metabolic homeostasis by dissipating energy via thermogenesis through uncoupling protein 1 (UCP1). Previously, we reported that the TATA-binding protein associated factor 7L (TAF7L) is an important regulator of white adipose tissue (WAT) differentiation. In this study, we show that TAF7L also serves as a molecular switch between brown fat and muscle lineages in vivo and in vitro. In adipose tissue, TAF7L-containing TFIID complexes associate with PPARγ to mediate DNA looping between distal enhancers and core promoter elements. Our findings suggest that the presence of the tissue-specific TAF7L subunit in TFIID functions to promote long-range chromatin interactions during BAT lineage specification.

GATA transcription factors as potentiators of gut endoderm differentiation

Development ◽  
1998 ◽  
Vol 125 (24) ◽  
pp. 4909-4917 ◽  
Author(s):  
P. Bossard ◽  
K.S. Zaret
Keyword(s):  
Gene Expression ◽  
Transcription Factors ◽  
Site Occupancy ◽  
Gata Factor ◽  
Transcriptional Enhancer ◽  
Gata Factors ◽  
Endoderm Differentiation ◽  
Albumin Gene ◽  
Gut Endoderm

Gene inactivation studies have shown that members of the GATA family of transcription factors are critical for endoderm differentiation in mice, flies and worms, yet how these proteins function in such a conserved developmental context has not been understood. We use in vivo footprinting of mouse embryonic endoderm cells to show that a DNA-binding site for GATA factors is occupied on a liver-specific, transcriptional enhancer of the serum albumin gene. GATA site occupancy occurs in gut endoderm cells at their pluripotent stage: the cells have the potential to initiate tissue development but they have not yet been committed to express albumin or other tissue-specific genes. The GATA-4 isoform accounts for about half of the nuclear GATA-factor-binding activity in the endoderm. GATA site occupancy persists during hepatic development and is necessary for the activity of albumin gene enhancer. Thus, GATA factors in the endoderm are among the first to bind essential regulatory sites in chromatin. Binding occurs prior to activation of gene expression, changes in cell morphology or functional commitment that would indicate differentiation. We suggest that GATA factors at target sites in chromatin may generally help potentiate gene expression and tissue specification in metazoan endoderm development.

scholarly journals Analysis of In-Vivo LacR-Mediated Gene Repression Based on the Mechanics of DNA Looping

PLoS ONE ◽  
2006 ◽  
Vol 1 (1) ◽  
pp. e136 ◽  
Author(s):  
Yongli Zhang ◽  
Abbye E. McEwen ◽  
Donald M. Crothers ◽  
Stephen D. Levene
Keyword(s):  
Dna Looping ◽  
Gene Repression

scholarly journals Autoimmune vitiligo is associated with gain-of-function by a transcriptional regulator that elevates expression of HLA-A*02:01 in vivo

2016 ◽  
Vol 113 (5) ◽  
pp. 1357-1362 ◽  
Author(s):  
Masahiro Hayashi ◽  
Ying Jin ◽  
Daniel Yorgov ◽  
Stephanie A. Santorico ◽  
James Hagman ◽  
...  
Keyword(s):  
High Risk ◽  
Mononuclear Cells ◽  
Risk Allele ◽  
Transcriptional Regulator ◽  
Class I ◽  
Strong Linkage Disequilibrium ◽  
Risk Haplotype ◽  
Transcriptional Enhancer ◽  
Gain Of Function

HLA-A is a class I major histocompatibility complex receptor that presents peptide antigens on the surface of most cells. Vitiligo, an autoimmune disease in which skin melanocytes are destroyed by cognate T cells, is associated with variation in the HLA-A gene; specifically HLA-A*02:01, which presents multiple vitiligo melanocyte autoantigens. Refined genetic mapping localizes vitiligo risk in the HLA-A region to an SNP haplotype ∼20-kb downstream, spanning an ENCODE element with many characteristics of a transcriptional enhancer. Convergent CTCF insulator sites flanking the HLA-A gene promoter and the predicted transcriptional regulator, with apparent interaction between these sites, suggests this element regulates the HLA-A promoter. Peripheral blood mononuclear cells from healthy subjects homozygous for the high-risk haplotype expressed 39% more HLA-A RNA than cells from subjects carrying nonhigh-risk haplotypes (P = 0.0048). Similarly, RNAseq analysis of 1,000 Genomes Project data showed more HLA-A mRNA expressed in subjects homozygous for the high-risk allele of lead SNP rs60131261 than subjects homozygous for the low-risk allele (P = 0.006). Reporter plasmid transfection and genomic run-on sequence analyses confirm that the HLA-A transcriptional regulator contains multiple bidirectional promoters, with greatest activity on the high-risk haplotype, although it does not behave as a classic enhancer. Vitiligo risk associated with the MHC class I region thus derives from combined quantitative and qualitative phenomena: a SNP haplotype in a transcriptional regulator that induces gain-of-function, elevating expression of HLA-A RNA in vivo, in strong linkage disequilibrium with an HLA-A allele that confers *02:01 specificity.

scholarly journals Minimal transcriptional enhancer of simian virus 40 is a 74-base-pair sequence that has interacting domains.

1986 ◽  
Vol 6 (11) ◽  
pp. 3667-3676 ◽  
Author(s):  
T A Firak ◽  
K N Subramanian
Keyword(s):  
Base Pair ◽  
Simian Virus 40 ◽  
Simian Virus ◽  
Proximal Region ◽  
Slight Reduction ◽  
Transcriptional Enhancer ◽  
Core Element ◽  
Enhancer Activity ◽  
Simplex Virus

We have assayed the ability of segments of the simian virus 40 (SV40) 72-base-pair (bp) repeat enhancer region to activate gene expression under the control of the SV40 early promoter and to compete for trans-acting enhancer-binding factors of limited availability in vivo in monkey CV-1 or human HeLa cells. The bacterial chloramphenicol acetyltransferase and the herpes simplex virus type 1 thymidine kinase genes were used as reporters in these assays. A 94-bp sequence located between SV40 nucleotides 179 and 272, including one copy of the 72-bp repeat, has been termed the minimal enhancer in previous studies. In the present study, we found that the 20-bp origin-proximal region located between nucleotides 179 and 198 was dispensable, since its removal caused only a slight reduction in enhancer activity. However, the deletion of another 4 bp up to nucleotide 202 abolished the enhancer activity. We propose that the minimal enhancer is a 74-bp sequence located between nucleotides 199 and 272, including 52 bp of one copy of the 72-bp repeat and a 22-bp adjacent sequence up to the PvuII site at 272. The nonamer 5'-AAGT/CATGCA-3', which we term the K core, occurred as a tandem duplication around the SphI site at nucleotide 200, and we found that this duplication was essential for enhancement and factor-binding activities. A heterologous core element (which we term the C core), 5'-GTGGA/TA/TA/TG-3', identified earlier (G. Khoury and P. Gruss, Cell 33:313-314, 1983; Weiher et al., Science 219:626-631, 1983) also occurred in duplicate, with one of the copies located within the 22-bp sequence near nucleotide 272 present outside the 72-bp repeat. We provide direct evidence that this 22-bp sequence augments enhancer activity considerably. We also found that in addition to the heterologous interaction occurring normally between the K and C cores within the minimal enhancer, certain homologous interactions were also permitted provided there was proper spacing between the elements.

scholarly journals Quantitation of the DNA tethering effect in long-range DNA looping in vivo and in vitro using the Lac and   repressors

2013 ◽  
Vol 111 (1) ◽  
pp. 349-354 ◽  
Author(s):  
D. G. Priest ◽  
L. Cui ◽  
S. Kumar ◽  
D. D. Dunlap ◽  
I. B. Dodd ◽  
...  
Keyword(s):  
Long Range ◽  
Dna Looping

scholarly journals Reconcilingin vitroandin vivoactivities of engineered, LacI-based repressor proteins: Contributions of DNA looping and operator sequence variation

2018 ◽  
Author(s):  
Sudheer Tungtur ◽  
Kristen M. Schwingen ◽  
Joshua J. Riepe ◽  
Chamitha J. Weeramange ◽  
Liskin Swint-Kruse
Keyword(s):  
Amino Acid ◽  
Dna Looping ◽  
Published Data ◽  
Binding Affinities ◽  
Ligand Specificity ◽  
Primary Operator ◽  
Repressor Proteins ◽  
Operator Sequence

AbstractOne way to create new components for synthetic transcription circuits is to re-purpose naturally occurring transcription factor proteins and their cognate DNA operators. For the proteins, re-engineering can be accomplished via domain recombination (to create chimeric regulators) and/or amino acid substitutions. The resulting activities of new protein regulators are often assessedin vitrousing a representative operator. However, when functioningin vivo, transcription factors can interact with multiple operators. We comparedin vivoandin vitroresults for two LacI-based transcription repressor proteins, their mutational variants, and four operator sequences. The two sets of repressor variants differed in their overallin vivorepression, even though theirin vitrobinding affinities for the primary operator spanned the same range. Here, we show that the offset can be explained by different abilities to simultaneously bind and “loop” two DNA operators. Furtherin vitrostudies of the looping-competent repressors were carried out to measure binding to a secondary operator sequence. Surprisingly, binding to this operator was largely insensitive to amino acid changes in the repressor protein.In vitroexperiments with additional operators and analyses of published data indicates that amino acid changes in these repressor proteins leads to complicated changes in ligand specificity. These results raise new considerations for engineering components of synthetic transcription circuits and – more broadly – illustrate difficulties encountered when trying to extrapolate information about specificity determinant positions among protein homologs.

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