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The promoter of inducible nitric oxide synthase implicated in glaucoma based on genetic analysis and nuclear factor binding.
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
2005 (Engelska)Ingår i: Molecular Vision, ISSN 1090-0535, Vol. 11, s. 950-957Artikel i tidskrift (Refereegranskat) Published
Ort, förlag, år, upplaga, sidor
2005. Vol. 11, s. 950-957
Identifikatorer
URN: urn:nbn:se:uu:diva-97861OAI: oai:DiVA.org:uu-97861DiVA, id: diva2:172950
Tillgänglig från: 2008-11-18 Skapad: 2008-11-18 Senast uppdaterad: 2023-02-03Bibliografiskt granskad
Ingår i avhandling
1. Genetic and Genomic Analysis of Transcriptional Regulation in Human Cells
Öppna denna publikation i ny flik eller fönster >>Genetic and Genomic Analysis of Transcriptional Regulation in Human Cells
2008 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
Abstract [en]

There are around 20.000 genes in the human genome all of which could potentially be expressed. However, it is obvious that not all of them can be active at the same time. Thus, there is a need for coordination achieved through the regulation of transcription. Transcriptional regulation is a crucial multi-component process involving genetic and epigenetic factors, which determine when and how genes are expressed. The aim of this thesis was to study two of these components, the transcription factors and the DNA sequence elements with which they interact.

In papers I and II, we tried to characterize the regulatory role of repeated elements in the regulatory sequences of nitric oxide synthase 2 gene. We found that this type of repeat is able to adopt non B-DNA conformations in vitro and that it binds nuclear factors, in addition to RNA polymerase II. Therefore it is probable that these types of repeats can participate in the regulation of genes.

In papers III-V, we intended to analyze the genome-wide binding sites for six transcription factors involved in fatty acid and cholesterol metabolism and the sites of an epigenetic mark in a human liver cell line. For this, we applied the chromatin immunoprecipitation (ChIP) method together with detection on microarrays (ChIP-chip) or by detection with the new generation massively parallel sequencers (ChIP-seq). We found that all of these transcription factors are involved in other liver-specific processes than metabolism, for example cell proliferation. We were also able to define two sets of transcription factors depending on the position of their binding relative to gene promoters. Finally, we demonstrated that the patterns of the epigenetic mark reflect the structure and transcriptional activity of the promoters.

In conclusion, this thesis presents experiments, which moves our view from genetics to genomics, from in vitro to in vivo, and from low resolution to high resolution analysis of transcriptional regulation.

Ort, förlag, år, upplaga, sidor
Uppsala: Acta Universitatis Upsaliensis, 2008. s. 64
Serie
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 403
Nyckelord
Transcription, ChIP-chip, ChIP-seq, genome-wide, transcription factors, microsatellite, epigenetic
Nationell ämneskategori
Medicinsk genetik
Identifikatorer
urn:nbn:se:uu:diva-9407 (URN)978-91-554-7355-6 (ISBN)
Disputation
2008-12-12, Rudbecksalen, Rudbecklaboratoriet, Uppsala, 09:15
Opponent
Handledare
Tillgänglig från: 2008-11-18 Skapad: 2008-11-18 Senast uppdaterad: 2022-03-11Bibliografiskt granskad

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