Transcription of the IL10 gene reveals allele-specific regulation at the mRNA level

ABSTRACT Many phenotypic differences exist between Homo sapiens and its closest relatives, chimpanzees, and these differences can arise as a result of variations in the regulation of certain genes common to these closely related species. Human-specific endogenous retroviruses (HERVs) and their solitary long terminal repeats (LTRs) are probable candidates for such a role due to the presence of regulatory elements, such as enhancers, promoters, splice sites, and polyadenylation signals. In this study we show for the first time that HERVs can participate in the specific antisense regulation of human gene expression owing to their LTR promoter activity. We found that two HERV LTRs situated in the introns of genes SLC4A8 (for sodium bicarbonate cotransporter) and IFT172 (for intraflagellar transport protein 172) in the antisense orientation serve in vivo as promoters for generating RNAs complementary to the exons of enclosing genes. The antisense transcripts formed from LTR promoter were shown to decrease the mRNA level of the corresponding genes. The human-specific regulation of these genes suggests their involvement in the evolutionary process.

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LncRNA Snhg6 regulates the differentiation of MDSCs by regulating the ubiquitination of EZH2

Journal of Hematology & Oncology ◽

10.1186/s13045-021-01212-0 ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Wei Lu ◽

Fenghua Cao ◽

Lili Feng ◽

Ge Song ◽

Yi Chang ◽

...

Keyword(s):

Bone Marrow ◽

Bone Marrow Cells ◽

Mrna Level ◽

Suppressor Cells ◽

Cell Group ◽

Mouse Bone Marrow ◽

Lewis Lung Cancer ◽

Bone Marrow Precursor ◽

Specific Regulation

AbstractMyeloid-derived suppressor cells (MDSCs) are derived from bone marrow progenitor cells commonly, which is a heterogeneous cell group composed of immature granulocytes, dendritic cells, macrophages and early undifferentiated bone marrow precursor cells. Its differentiation and immunosuppressive function are regulated by complex network signals, but the specific regulation mechanisms are not yet fully understood. In this study, we found that in mouse of Lewis lung cancer xenograft, long non-coding RNA Snhg6 (lncRNA Snhg6) was highly expressed in tumor-derived MDSCs compared with spleen-derived MDSCs. LncRNA Snhg6 facilitated the differentiation of CD11b+ Ly6G− Ly6Chigh monocytic MDSCs (Mo-MDSCs) rather than CD11b+ Ly6G+ Ly6Clow polymorphonuclear MDSCs (PMN-MDSCs), but did not affect the immunosuppressive function of MDSCs. Notably, lncRNA Snhg6 could inhibit the expression of EZH2 by ubiquitination pathway at protein level rather than mRNA level during the differentiation of mouse bone marrow cells into MDSCs in vitro. EZH2 may be an important factor in the regulation of lncRNA Snhg6 to promote the differentiation of Mo-MDSCs. So what we found may provide new ideas and targets for anti-tumor immunotherapy targeting MDSCs.

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Abstract P117: Blood Pressure Heterosis And Genotype-Specific Regulation Of C17h6orf52

Hypertension ◽

10.1161/hyp.76.suppl_1.p117 ◽

2020 ◽

Vol 76 (Suppl_1) ◽

Author(s):

Karen C Clark ◽

Valerie Wagner ◽

Anne E Kwitek

Keyword(s):

Blood Pressure ◽

Hybrid Vigor ◽

Female Rats ◽

Lower Systolic Blood Pressure ◽

Male And Female Rats ◽

Protein Functions ◽

Show Evidence ◽

Normal Chow ◽

Allele Specific ◽

Specific Regulation

Although blood pressure (BP) is highly heritable, the genetic etiology is complex, and causative genes do not completely explain observed variation. Using the Lyon Hypertensive (LH) rat—a well-characterized polygenic inbred model—we previously identified a novel candidate gene ( C17h6orf52 ) as a master regulator of gene expression regulating cardiometabolic traits. CRISPR-Cas9 gene editing was used to generate a mutation in C17h6orf52 , and blood pressure in homozygous wildtype (WT), heterozygous (HET) and homozygous mutant (MUT) females was characterized via radiotelemetry. Herein, we show evidence of BP heterosis (i.e. hybrid vigor) in females from the C17h6orf52 strain. Systolic (SBP) and diastolic (DBP) pressures (mmHg) were determined in WT, HET, and MUT male and female rats on normal chow (CHOW), and 4% salt (NaCl) diet (to determine salt sensitivity). All measures are presented as mean±SEM, and significant results are indicated according to statistical test. No significant differences were identified in males, but the HET females (n=5) had significantly lower systolic blood pressure than either WT (n=7) or MUT (n=8) at both baseline and salt-stressed conditions: SBP-CHOW: (WT: 144±3.28; HET: 136.0±0.83 * ; MUT: 142.6±2.13)DBP-CHOW: (WT: 98.3±2.29; HET: 94.0±0.68; MUT: 97.4±1.76)SBP-NaCl: (WT: 150.4±3.40; HET: 142.2±1.19 * ; MUT: 150.2±1.83)DBP-NaCl: (WT: 103.3±2.75; HET: 98.2±1.68; MUT: 103.1±1.68) Tissues were collected to assess C17h6orf52 expression relative to WT, displayed below as confidence intervals. While there were no differences between WT and MUT expression, liver C17h6orf52 was significantly overexpressed in heterozygous females. C17h6orf52 2^-ddCT: (WT: 0.91-1.09, n=8; HET: 1.33-1.73 $ , n=5; MUT: 0.85-1.19, n=8) There were no striking differences in any metabolic phenotypes, such as body weight and adiposity, thus these data suggest that C17h6orf52 is protective against increases in blood pressure specifically. Continued study will attempt to tease apart allele-specific regulation and protein functions in heterozygous animals of both sexes. * p<0.05 by Kruskal-Wallis $ p<0.05 by 1-WAY ANOVA

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Inhibition of MMP Synthesis by Doxycycline and Chemically Modified Tetracyclines (CMTs) in Human Endothelial Cells

Advances in Dental Research ◽

10.1177/08959374980120010301 ◽

1998 ◽

Vol 12 (1) ◽

pp. 114-118 ◽

Cited By ~ 139

Author(s):

R. Hanemaaijer ◽

H. Visser ◽

P. Koolwijk ◽

T. Sorsa ◽

T. Salo ◽

...

Keyword(s):

Endothelial Cells ◽

Western Blotting ◽

Broad Spectrum ◽

Mrna Level ◽

Gelatin Zymography ◽

Human Endothelial Cells ◽

Broad Spectrum Antibiotic ◽

Chemically Modified ◽

Specific Regulation ◽

Chemically Modified Tetracyclines

Doxycycline is a commonly used broad-spectrum antibiotic. Recently, it has been shown that it also inhibits the activity of mammalian collagenases and gelatinases, an activity unrelated to its antimicrobial efficacy. In this study, we show that doxycycline not only inhibits MMP-8 and MMP-9 (gelatinase B) activity, but also the synthesis of MMPs in human endothelial cells. Doxycycline (50 μM) completely inhibited the phorbol-12-myristate-13-acetate (PMA)-mediated induction of MMP-8 and MMP-9, as measured by Western blotting and gelatin zymography, respectively. The inhibition was also observed at the mRNA level. No effect was observed on the expression of MMP-2 and of the MMP inhibitors TIMP-1 and TIMP-2. Chemically modified tetracyclines (CMTs) showed an inhibition similar to that of doxycycline, albeit less efficient. These observations demonstrate that endothelial cells display a specific regulation of MMPs, which may have implications for the pharmaceutical interaction in angiogenesis and angiogenesis-related diseases.

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