[Todos FBMC] Seminario DFBMC-IFIBYNE - Dr. Ezequiel Nazer - Jueves 16 de noviembre - 13:00 hs - Aula Seminarios LFBM

Seminarios FBMC seminarios-FBMC en fbmc.fcen.uba.ar
Lun Nov 13 08:02:45 ART 2017


Buenos días,

Quedan cordialmente invitados al próximo seminario DFBMC-IFIBYNE, a
realizarse el jueves 16 de noviembre a las 13 hs en el Aula de Seminarios
del LFBM, Pabellón II, 2º piso.

Expone: Ezequiel Nazer, Ph.D.

Título: "Argonaute2 and LaminB repress transcription by controlling RNA
Polymerase II recruitment and chromatin topology in Drosophila
melanogaster".

Resumen:

Argonaute proteins correspond to an evolutionarily conserved protein
family engaged in gene silencing. The RNA interference (RNAi) pathway
effector protein Argonaute2 (AGO2) interacts with small RNAs to regulate
gene silencing in the cytoplasm. In addition, AGO2 has been shown to
regulate gene expression by functioning in the nucleus. Previous work
showed that Drosophila AGO2 is preferentially associated with active
promoters and can activate gene expression by promoting chromatin looping
to an enhancer. Interestingly, this function was shown to be completely
RNAi-independent. To gain molecular insights into AGO2 in regulating
transcription, we performed mass spec to identify factors that interact
with AGO2 in nuclear extracts and found RNA Polymerase II (Pol II) and
LaminB among the top-associated proteins. By using nascent RNA sequencing
(neuRNA-seq) we found that AGO2 and LaminB co-repress transcription at
borders between LaminB-associated domains (LAD) and
topologically-associated domains (TADs), which are highly self-interacting
genomic regions that tend to be either transcriptionally active or
inactive. To ensure that changes in transcription were not due to defects
in the RNAi pathway, we performed neuRNA-seq analysis upon Dicer2
depletion and did not observe similar transcriptome changes in comparison
to AGO2.Differential ChIP-seq analysis for a large number of factors and
histone modifications revealed that AGO2 and LaminB specifically control
Pol II recruitment at regulated genes, but in a differential manner.
Specifically, LaminB prevents Pol II recruitment while AGO2 limits both
Pol II initiation as well as its transition into productive elongation. To
investigate the physiological role of AGO2-mediated transcriptional
repression, we carried out mRNA-seq from AGO2 mutant whole female larvae.
We found that both AGO2 and LaminB repress transcription of no hitter
(nht), a master regulator of the spermatogenesis gene program, in somatic
cells. Finally, 4C-seq analysis showed that AGO2 and LaminB modulate the
chromatin topology of the TAD/LAD in which nht is embedded. We conclude
that AGO2 and LaminB work in concert to regulate gene expression by
orchestrating overall genome organization, thus contributing to
transcriptionally modulate a key developmental process such as
spermatogenesis.


Esperamos contar con vuestra presencia. ¡Muchas gracias!


Ministerio de seminarios DFBMC-IFIBYNE
Francisco Urbano
Mariana Feld
Cecilia D'Alessio




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