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Cross-talk between signaling pathway and histone modifications in response to growth factor stimulation

Grant number: 17/15835-1
Support type:Scholarships abroad - Research Internship - Doctorate (Direct)
Effective date (Start): November 01, 2017
Effective date (End): October 31, 2018
Field of knowledge:Biological Sciences - Biochemistry
Principal researcher:Julia Pinheiro Chagas da Cunha
Grantee:Mariana de Camargo Lopes
Supervisor abroad: Benjamin Aaron Garcia
Home Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
Research place: University of Pennsylvania, United States  
Associated to the scholarship:16/24881-4 - Nuclear proteome alterations induced by growth factor along cell cycle in mice tumour cells, BP.DD


Despite being a growth factor, FGF-2 has anti-proliferative and tumor suppressive functions in some cellular contexts. In a murine adrenocortical tumor cell line (lineage Y1), FGF-2 triggers an initial mitogenic response through ERK1/2, PKC and AKT signaling but results in a G2/M cell cycle arrest through RhoA/GTP-src signaling. Recently, we found transcription factors related to early-gene responses (such as fosB and junB) that are differentially expressed after FGF-2 treatment. We also found a global decrease in chromatin active marks, such as acetylations of histone H4 N-terminus after 3 hours of FGF-2 stimulation. To better understand the dual phenotypic response (mitogenic versus cell cycle arrest) induced by FGF-2 we aim to perform a time-course quantitative proteomics analysis of histone PTMs and phosphoproteomics upon serum and FGF-2 stimulation in the Y1 cell line. An integration between signaling pathways and epigenetic changes induced by serum and/or FGF-2 will be performed in a systems biology perspective using bioinformatics tools. To our knowledge, high throughput analysis of cell signaling activation integrated to histone PTMs dynamics have been poorly explored in literature despite their importance in gene regulation. We believe that our work will shed light on how signaling pathways may interact with histone PTMs in both proliferative (serum stimulated cells) and non-proliferative (FGF-2 stimulated cells) responses. (AU)

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Scientific publications (4)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
SIDOLI, SIMONE; LOPES, MARIANA; LUND, PEDER J.; GOLDMAN, NAOMI; FASOLINO, MARIA; CORADIN, MARIEL; KULEJ, KATARZYNA; BHANU, V, NATARAJAN; VAHEDI, GOLNAZ; GARCIA, BENJAMIN A.. A mass spectrometry-based assay using metabolic labeling to rapidly monitor chromatin accessibility of modified histone proteins. SCIENTIFIC REPORTS, v. 9, . (17/15835-1)
LIU, XIAOJING; COOPER, DANIEL E.; CLUNTUN, AHMAD A.; WARMOES, MARC O.; ZHAO, STEVEN; REID, MICHAEL A.; LIU, JUAN; LUND, PEDER J.; LOPES, MARIANA; GARCIA, BENJAMIN A.; et al. Acetate Production from Glucose and Coupling to Mitochondrial Metabolism in Mammals. Cell, v. 175, n. 2, p. 502+, . (17/15835-1)
SIDOLI, SIMONE; KORI, YEKATERINA; LOPES, MARIANA; YUAN, ZUO-FEI; KIM, HEE JONG; KULEJ, KATARZYNA; JANSSEN, KEVIN A.; AGOSTO, LAURA M.; CHAGAS DA CUNHA, JULIA PINHEIRO; ANDREWS, ANDREW J.; et al. One minute analysis of 200 histone posttranslational modifications by direct injection mass spectrometry. Genome Research, v. 29, n. 6, p. 978-987, . (17/15835-1)
LUND, PEDER J.; LOPES, MARIANA; SIDOLI, SIMONE; CORADIN, MARIEL; DE LUNA VITORINO, FRANCISCA NATHALIA; CHAGAS DA CUNHA, JULIA PINHEIRO; GARCIA, BENJAMIN A.. FGF-2 induces a failure of cell cycle progression in cells harboring amplified K-Ras, revealing new insights into oncogene-induced senescence. MOLECULAR OMICS, v. 17, n. 5, p. 725-739, . (16/24881-4, 15/04867-4, 13/07467-1, 17/15835-1, 18/15553-9, 11/22619-7, 17/18344-9)

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