β hemoglobiniopathies (Sickle cell Anemia (SCA) and β-thalassemias) are genetic diseases caused by mutations in the β-globin gene, resulting in a defective production of the adult hemoglobin (HbA; α2β2) tetramer. Coinheritance of hereditary persistence of fetal hemoglobin (HbF α2γ2) expression greatly ameliorates the clinical symptoms in these patients. Thus, understanding the molecular mechanisms underlying the γ to β switch is important to design strategies for the pharmacological up-regulation of γ globin. Sox6 is a Transcription Factor with a crucial role in terminal erythroid maturation and in the hemoglobin fetal/adult switching. Sox6 can act both as transcriptional activator or repressor, but it lacks any conventional activator or repression domain, suggesting that Sox6 has to interact with other proteins or complexes to exert its function. To draw a map of Sox6 interactors in erythroid cells, we undertook the purification of Sox6 complexes by using a biotynilation-tagging approach followed by Mass-Spectrometry in human erythroleukemic HEL cells. Sox6 was found to interact with multiprotein complexes consisting of chromatin remodeling factors, transcriptional corepressors, cyclines dependent kinases (CDKs) and erythroid transcription factors. In particular, Sox6 interacts with most of the subunits of the chromatin-remodeling co-repression NurD (Nucleosome Remodeling Deacetylase) complex. The knockdown of some of these interactors by siRNA transfection in erythroid cells confirms a crucial role of Sox6 complexes in erythroid differentiation and globin genes regulation.
(2015). Identification and characterization of protein complexes including the transcription factor Sox6 in erythroid cells. (Tesi di dottorato, Università degli Studi di Milano-Bicocca, 2015).
RONCHI, ANTONELLA ELLENA
|Data di pubblicazione:||25-giu-2015|
|Titolo:||Identification and characterization of protein complexes including the transcription factor Sox6 in erythroid cells|
|Settore Scientifico Disciplinare:||BIO/18 - GENETICA|
|Scuola di dottorato:||Scuola di Dottorato in Medicina Traslazionale e Molecolare|
|Corso di dottorato:||SCUOLA DI DOTTORATO IN MEDICINA TRASLAZIONALE E MOLECOLARE (DIMET) - 72R|
|Citazione:||(2015). Identification and characterization of protein complexes including the transcription factor Sox6 in erythroid cells. (Tesi di dottorato, Università degli Studi di Milano-Bicocca, 2015).|
|Parole Chiave (Inglese):||erythropoiesis; transcription factors; affinity-tag; purification|
|Appare nelle tipologie:||07 - Tesi di dottorato Bicocca post 2009|