| Grant number: | 17/20847-9 |
| Support Opportunities: | Scholarships abroad - Research Internship - Doctorate |
| Start date: | March 01, 2018 |
| End date: | February 28, 2019 |
| Field of knowledge: | Health Sciences - Medicine - Medical Clinics |
| Principal Investigator: | Maria Isabel de Souza Aranha Melaragno |
| Grantee: | Adriana di Battista |
| Supervisor: | Alexandre Reymond |
| Host Institution: | Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil |
| Institution abroad: | Université de Lausanne (UNIL), Switzerland |
| Associated to the scholarship: | 16/22860-0 - Investigation of chromatin remodelling in balanced X-autosome translocations and its influence on phenotype, BP.DR |
Abstract The impact of three-dimensional chromatin organization in genetic regulation has been target of many research groups around the world. Chromosome territories are formed from chromatin organization and they are directly related to gene expression and regulation. Balanced chromosomal rearrangements may act through perturbations of the normal contacts between genes and their regulatory elements and changes of the overall chromatin topology.The study of patients with phenotypic alterations and balanced chromosome translocations with no gene disruption at the breakpoints can help in elucidating the repositioning effect of chromosome segments on gene expression regulation. Previous researches have described a strong relation between premature ovarian failure and balanced X-autosome translocation with breakpoints between Xq13 and Xq21. However, the pathogenic mechanism that affects the ovary development in these patients has not been elucidated yet, since gene disruptions do not explain the ovarian failure in the vast majority of cases. Moreover, women with Xq21 deletions are usually fertile, suggesting that the ovarian failure is not caused by copy number alterations in that region. Thus, a position effect is the main hypothesis to explain the genetic mechanism responsible for premature ovarian failure in women with translocation between an autosome chromosome and one of their X chromosomes.We propose to investigate the three-dimensional structure of chromatin and its effect on gene expression in patients with balanced X-autosomes translocations and premature ovarian failure, by combining RNA-seq, ChIP-seq, 4C-seq, 3D DNA-FISH and Immuno DNA-FISH. This study proposes an innovative approach to investigate the impact of chromatin remodeling on gene expression regulation when the genome is subjected to a drastic transpositions of genomic material. The results obtained may provide a better understanding of the complex mechanism of gene regulation related to the chromatin organization in the interphase nucleus, as well as ovarian failure. | |
| News published in Agência FAPESP Newsletter about the scholarship: | |
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