Tissue- and stage-specific roles of the ubiquitously expressed transcription factor sp1 in haematopoietic development

Sp 1 is a ubiquitously expressed transcription factor and regulates a range of genes including housekeeping and tissue-specific genes. Studies using a DNA binding domain (DBD)-deficient Spl have shown that Spl is required for haematopoietic specification. Here, we generated a Spl-DBD deficient ESC line to recapitulate the previous model, as well as a novel Spl null ESC line. Spl knockout cells demonstrated a complete absence ofhaematopoietic differentiation, indicating a crucial role for Sp 1 at the early stages of blood cell specification. In contrast, Sp 1 DBD-deficient cells were able to differentiate to haematopoietic progenitors, but failed to terminally differentiate, suggesting a different mechanism of Sp !-mediated transcriptional regulation in early and later stages. Gene expression analysis in Spl knockout cells indicated a novel role for Spl in ESC differentiation potential and mesoderm formation, while chromatin accessibility profiling revealed changes in chromatin structure in the absence ofSpl. We found Sp3, a close family member ofSpl , is able to compensate for loss ofSpl at most sites, but not at some important genes encoding developmental regulators. This work provides novel insights into the interplay between Sp 1 and Sp3 and furthers our understanding of the function of one of the earliest discovered TFs

The Role of the Ubiquitously Expressed Transcription Factor Sp1 in Tissue-specific Transcriptional Regulation and in Disease

Sp1 belongs to the 26 member strong Sp/KLF family of transcription factors. It is a paradigm for a ubiquitously expressed transcription factor and is involved in regulating the expression of genes associated with a wide range of cellular processes in mammalian cells. Sp1 can interact with a range of proteins, including other transcription factors, members of the transcription initiation complex and epigenetic regulators, enabling tight regulation of its target genes. In this review, we discuss the mechanisms involved in Sp1-mediated transcriptional regulation, as well as how a ubiquitous transcription factor can be involved in establishing a tissue-specific pattern of gene expression and mechanisms by which its activity may be regulated. We also consider the role of Sp1 in human diseases, such as cancer

Clonal expansion within pneumococcal serotype 6C after use of seven-valent vaccine

Streptococcus pneumoniae causes invasive infections, primarily at the extremes of life. A seven-valent conjugate vaccine (PCV7) is used to protect against invasive pneumococcal disease in children. Within three years of PCV7 introduction, we observed a fourfold increase in serotype 6C carriage, predominantly due to a single clone. We determined the whole-genome sequences of nineteen S. pneumoniae serotype 6C isolates, from both carriage (n = 15) and disease (n = 4) states, to investigate the emergence of serotype 6C in our population, focusing on a single multi-locus sequence type (MLST) clonal complex 395 (CC395). A phylogenetic network was constructed to identify different lineages, followed by analysis of variability in gene sets and sequences. Serotype 6C isolates from this single geographical site fell into four broad phylogenetically distinct lineages. Variation was seen in the 6C capsular locus and in sequences of genes encoding surface proteins. The largest clonal complex was characterised by the presence of lantibiotic synthesis locus. In our population, the 6C capsular locus has been introduced into multiple lineages by independent capsular switching events. However, rapid clonal expansion has occurred within a single MLST clonal complex. Worryingly, plasticity exists within current and potential vaccine-associated loci, a consideration for future vaccine use, target selection and design

Synthese und Struktur eines stabilen 16-Elektronen-α-Acyl-Esterenolat-Iridium(III) -Komplexes (Cl)(Ph3P)2I

Eliminierung von HCl aus dem sechsfach koordinierten Komplex Cl2(Ph3P)2 liefert den α-Acylesterenolat-Komplex (Cl)Ph3P)2 (1) mit der Koordinationszahl 5. Die Röntgenstrukturanalyse zeigt für 1 eine verzerrte tetragonal pyramidale Struktur mit der Acylgruppe an der Spitze. An den 16-Elektronen-Komplex 1 lassen sich (reversibel) CO und CH3CN addieren

Feasibility Study Youth Work Funding Review: Phase 1, Feasibility Study Report

This report presents the findings from the first phase of a review of youth work funding in Wales carried out on behalf of the Welsh Government, Youth Engagement Branch (WGYEB). The work of the Interim Youth Work Board (IYWB) provides the background to this research. In 2018 the Board was tasked with developing recommendations aimed at achieving a sustainable delivery model for youth work in Wales, and these have provided the impetus for this research. The fourth of its 14 recommendations was to undertake an independent review into the sufficiency, transparency, accountability and effectiveness of funding and expenditure on youth work services across the Welsh Government, local authorities, and voluntary organisations, to assess the effective delivery of outcomes and impact for young people

Astudiaeth Ddichonoldeb Adolygiad o Ariannu Gwaith Ieuenctid Crynodeb Gweithredol

Mae’r adroddiad hwn yn cyflwyno canfyddiadau astudiaeth ddichonoldeb o adolygiad o gyllid gwaith ieuenctid yng Nghymru a gynhaliwyd ar ran Llywodraeth Cymru, y Gangen Ymgysylltu Ieuenctid (WGYEB). Rhwng 2018-2021 cafodd y Bwrdd Gwaith Ieuenctid Interim (BGII) y cyfrifoldeb o ddatblygu argymhellion ar gyfer model cynaliadwy ar gyfer gwaith ieuenctid yng Nghymru. Eu hadroddiad terfynol `Mae’n Bryd Cyflawni dros Bobl Ifanc yng Nghymru’ oedd y symbyliad ar gyfer yr ymchwil hwn. Dywed y pedwerydd o 14 argymhelliad y Bwrdd y: “Dylai Llywodraeth Cymru […] gynnal adolygiad annibynnol i ddigonolrwydd, tryloywder, atebolrwydd ac effeithiolrwydd cyllid a gwariant ar wasanaethau gwaith ieuenctid ar draws Llywodraeth Cymru, awdurdodau lleol a mudiadau gwirfoddol, er mwyn asesu sut y darparwyd deilliannau ac effaith ar gyfer pobl ifanc” (Bwrdd Gwaith Ieuenctid Interim, 2021)

Feasibility Study: Youth Work Funding Review Executive Summary

This report presents the findings from a feasibility study of a review of youth work funding in Wales carried out on behalf of the Welsh Government, Youth Engagement Branch (WGYEB). From 2018-2021 the Interim Youth Work Board (IYWB) was tasked with developing recommendations for a sustainable model for youth work in Wales. Their final report `Time to Deliver for young people in Wales’ provided the impetus for this research. The fourth of the Board’s 14 recommendations was that: “Welsh Government should […] undertake an independent review into the sufficiency, transparency, accountability, and effectiveness of funding and expenditure on youth work services across Welsh Government, local authorities, and voluntary organisations, to assess the effective delivery of outcomes and impact for young people” (Interim Youth Work Board, 2021)

Astudiaeth Ddichonoldeb Adolygiad o Ariannu Gwaith Ieuenctid

Mae’r adroddiad hwn yn cyflwyno canfyddiadau cam cyntaf adolygiad o arian gwaith ieuenctid yng Nghymru a gynhaliwyd ar ran Llywodraeth Cymru, Cangen Ymgysylltu ag Ieuenctid (CYILlC). Mae gwaith y Bwrdd Gwaith Ieuenctid Interim yn darparu’r cefndir i’r ymchwil hwn. Yn 2018 gofynnwyd i’r Bwrdd ddatblygu argymhellion ar gyfer sicrhau model cyflawni cynaliadwy ar gyfer gwaith ieuenctid yng Nghymru, a’r argymhellion hyn a symbylodd yr ymchwil hwn. Y pedwerydd o’i 14 argymhelliad oedd cynnal adolygiad annibynnol i ddigonolrwydd, tryloywder, atebolrwydd ac effeithiolrwydd cyllid a gwariant ar wasanaethau gwaith ieuenctid ar draws Llywodraeth Cymru, awdurdodau lleol a mudiadau gwirfoddol, er mwyn asesu sut y darparwyd deilliannau ac effaith ar gyfer pobl ifanc