2024-03-28T19:57:11Zhttps://www.tdx.cat/oai/requestoai:www.tdx.cat:10803/6732402024-03-15T10:57:15Zcom_10803_236col_10803_690278
nam a 5i 4500
MacroH2A
BAZ1A
MDS
CHARC
LINEs
Role of histone variant macroH2A and other chromatin regulators in genome regulation and response to drugs
:
,
2022
Accés lliure
http://hdl.handle.net/10803/673240
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Le Pannérer, Marguerite-Marie,
autor
Programa de doctorat en Biomedicina,
degree
1 recurs en línia (227 pàgines)
Tesi
Doctorat
Universitat Pompeu Fabra. Departament de Ciències Experimentals i de la Salut
2022
Universitat Pompeu Fabra. Departament de Ciències Experimentals i de la Salut
Tesis i dissertacions electròniques
Buschbeck, Marcus,
supervisor acadèmic
TDX
The relevance of epigenetics is increasingly recognized in haematopoietic diseases such as myelodysplastic syndromes (MDS) and acute myeloid leukaemia (AML). Variants of histones, such as macroH2As, and chromatin remodellers, such as the CHRAC complex, are key players in these epigenetic regulations. On the other hand, non-coding DNA regions, including long interspersed nuclear elements (LINEs), also show increasing relevance, notably in cancer.
Here, we studied the relationship between LINEs and macroH2As in a hepatocarcinoma cell line. Computational analysis and experimental work led to conflicting results regarding a potential repressive role of macroH2As on LINEs. In addition, we studied the role of macroH2As as well as other chromatin regulators in the response to the epigenetic treatments Azacitidine and Decitabine in MDS/AML cell lines and a cohort of patient's samples. We were able to show that reduced expression of macroH2A1 and CHRAC complex component, BAZ1A, sensitized MDS/AML cell lines to epigenetic treatments. Furthermore, in patient sample, CHRAC complex components were less expressed in ten-eleven translocase 2 (TET2) mutants and in non-responders to Azacitidine.
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