Tesis doctoral de Mónica Sancho Medina
At least eleven histone h1 variants exist in mammalian cells that bind to the linker dna and stabilize the nucleosome particle contributing to higher order chromatin compaction. In addition to playing a structural role, h1 seems to be involved in the activation and repression of gene expression. It is not well known whether the different variants have specific roles or regulate specific promoters. We have explored this by inducible shrna-mediated knock-down of five somatic h1 variants in a human breast cancer cell line. Rapid inhibition of each h1 variant was not compensated for changes of expression of other variants. A different subset of genes is altered in each h1 knock-down. Interestingly, h1.2 depletion represses expression of a number of cell cycle genes. This is concomitant with a g1 arrest phenotype observed in this cell line. In addition, h1.2 depletion caused decreased global nucleosome spacing. These effects are specific to h1.2 depletion as they are not complemented by overexpression of other variants and they do not occur in knock-downs for the other variants. Moreover, h1.4 depletion caused cell death in t47d, being the first report of the essentiality of an h1 variant for survival in a human cell type.%&/In addition to this, we have also investigated specificities of h1 subtypes location in particular promoters of interest in our laboratory, as well as specific interactions with other factors by generating ha-tagged h1 variant expressing cell lines.
Datos académicos de la tesis doctoral «Role of linker histone h1 variants in cell proliferation, chromatin structure and gene expression in breast cancer cells«
- Título de la tesis: Role of linker histone h1 variants in cell proliferation, chromatin structure and gene expression in breast cancer cells
- Autor: Mónica Sancho Medina
- Universidad: Pompeu fabra
- Fecha de lectura de la tesis: 30/05/2008
Dirección y tribunal
- Director de la tesis
- Albert Jordan Valles
- Tribunal
- Presidente del tribunal: ferran Azorin marin
- inmaculada Ponte marull (vocal)
- alejandro Vaquero garcia (vocal)
- oriol Bachs valldeneu (vocal)