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Pituitary enhancers SIGNED

Identification and functional validation of novel enhancer sequences involved in pituitary gland development and pathology

Total Cost €

0

EC-Contrib. €

0

Partnership

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 Pituitary enhancers project word cloud

Explore the words cloud of the Pituitary enhancers project. It provides you a very rough idea of what is the project "Pituitary enhancers" about.

gpr10    silico    indicator    mechanisms    accessibility    profile    preliminary    chip    conducting    perform    vitro    sanger    sequences    creation    histone    tested    transcription    hypothesis    linked    normal    methylation    seq    duplications    verified    transcriptional    putative    molecular    luciferase    acrogigantism    cnv    functionally    regulates    physiological    health    pathologies    de    remarkably    screen    interactions    enhancers    sequencing    novo    cells    pituitary    gene    clinical    pursuing    validate    functional    elucidate    there    region    reporter    chromatin    structural    mutations    genome    local    regulatory    enhancer    duplicated    marks    gap    gpr101    fundamental    disrupt    variations    pathological    central    underlying    structure    4c    showing    performed    tumors    tumoral    human    children    causing    located    disorders    expression    abnormal    promoter    domain    overexpression    assays    lag    regulation    patients    characterization    place   

Project "Pituitary enhancers" data sheet

The following table provides information about the project.

Coordinator
HUMANITAS MIRASOLE SPA 

Organization address
address: VIA MANZONI 56
city: ROZZANO (MI)
postcode: 20100
website: www.humanitas.it

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country Italy [IT]
 Total cost 183˙473 €
 EC max contribution 183˙473 € (100%)
 Programme 1. H2020-EU.1.3.2. (Nurturing excellence by means of cross-border and cross-sector mobility)
 Code Call H2020-MSCA-IF-2018
 Funding Scheme MSCA-IF-EF-RI
 Starting year 2020
 Duration (year-month-day) from 2020-03-16   to  2022-03-15

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    HUMANITAS MIRASOLE SPA IT (ROZZANO (MI)) coordinator 183˙473.00

Map

 Project objective

There is a fundamental gap in understanding how the GPR101 gene regulates human growth in physiological and pathological conditions. Children’s growth is remarkably clinical relevant and is an important indicator of their health and general well-being. The specific objective of this proposal is to identify the molecular mechanisms underlying GPR101 overexpression in the pituitary tumors of children with GPR101 duplications causing X-linked acrogigantism (X-LAG). My central hypothesis is that GPR101 duplications disrupt the structure of the local chromatin, leading to the creation of a new chromatin domain where de novo enhancer-promoter interactions take place, causing abnormal GPR101 expression. This hypothesis will be tested by pursuing three specific aims: 1. Elucidate the transcriptional regulation of GPR101 in normal and pathological conditions 2. Identify and functionally characterize novel pituitary-specific enhancer sequences 3. Investigate these regulatory sequences in patients with different pituitary pathologies. To achieve aim 1) I will perform an in vitro functional characterization of GPR101 promoter: promoter activity will be studied by luciferase-based reporter assays, by conducting a methylation analysis, and by determining its accessibility to transcription factors. To achieve aim 2) I will validate my preliminary results showing the formation of a novel chromatin domain by 4C-Seq. Four putative enhancer sequences located within the duplicated GPR10 region and identified in silico will be functionally evaluated in vitro to establish their impact on transcriptional activity. To identify novel pituitary-specific enhancers, a whole-genome profile of enhancer-specific histone marks will be performed in normal and tumoral pituitary cells by ChIP-Seq. To achieve aim 3) I will screen patients with different pituitary disorders for mutations (Sanger sequencing) and structural variations (CNV assays) in the functionally-verified enhancers.

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The information about "PITUITARY ENHANCERS" are provided by the European Opendata Portal: CORDIS opendata.

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