Systematic Approach to Dissect the Interplay between Chromatin and Transcription

Obiettivo

Epigenetic mechanisms play an important role in regulating and maintaining the functionality of cells and have been implicated in a wide range of human diseases. Histone proteins that form the protein core of nucleosomes are subject to a bewildering array of covalent and structural modifications, which can repress, permit, or promote transcription. These modifications can be added and removed by specialized complexes that are recruited by other covalent modifications, by transcription factors, or by the transcriptional machinery. Advances in genomics led to comprehensive mapping of the ``epigenome'' in a range of tissues and organisms. These maps established the tight connection between histone modifications and transcription programs. These static charts, however, are less successful at uncovering the underlying mechanisms, logic, and function of histone modifications in establishing and maintaining transcriptional programs. Our premise is that we can answer these basic questions by observing the effect of genetic perturbations on the dynamics of both chromatin state and transcriptional activity. We aim to dissect the chromatin-transcription system in a systematic manner by building on our extensive experience in modeling and analysis, and a unique high-throughput experimental system we established in my lab.

We plan to use the budding yeast model organism, which allows for
efficient genetic and experimental manipulations. We will combine two technologies: (1) high-throughput measurements of single-cell
transcriptional output using fluorescence reporters; and (2) high-throughput immunoprecipitation sequencing assays to map chromatin state. Measuring with these the dynamics of response to stimuli under different genetic backgrounds and using advanced stochastic network models, we will chart detailed mechanisms that are opaque to current approaches and elucidate the general principles that govern the interplay between chromatin and transcription.

Campo scientifico

Meccanismo di finanziamento

ERC-AG - ERC Advanced Grant

Istituzione ospitante

THE HEBREW UNIVERSITY OF JERUSALEM

Contributo UE

€ 2 396 450,00

Indirizzo

EDMOND J SAFRA CAMPUS GIVAT RAM
91904 Jerusalem
Israele

Tipo di attività

Higher or Secondary Education Establishments

Ricercatore principale

Nir Friedman (Prof.)

Contatto amministrativo

Hani Ben-Yehuda (Ms.)

Collegamenti

Contatta l’organizzazione Sito web

Costo totale

Nessun dato

Beneficiari (1)