Alessandro Gardini, Ph.D.

Research Summary

The Gardini lab investigates how global transcription is regulated during cell differentiation and oncogenesis using a variety of genomics and biochemistry approaches.

Transcription of coding and noncoding genes by RNA Polymerase II (RNAPII) is regulated at several steps: a) transcription factors and chromatin remodelers determine chromatin accessibility and recruitment of the basal transcription machinery; b) RNAPII processivity is determined by a set of elongation factors such as the PAF, Integrator and Super Elongation complexes; c) distal DNA regulatory elements known as ‘enhancers’ establish chromatin loops with neighboring genes and ultimately control RNAPII recruitment and stimulus-dependent gene activation.

There are three major lines of research in the lab:
1 - Role of enhancer and enhancer-derived noncoding RNAs during normal hematopoiesis and leukemia.
2 - Role of chromatin remodelers in ovarian cancer.
3 - Functional dissection of the Integrator protein complex during RNAPII elongation and processing of noncoding RNAs.

We integrate genome-wide techniques (such as ChIP-seq, RNA-seq, ATAC-seq and Global RunOn --GRO-seq-- ) with affinity purification of transcriptional regulatory complexes to assess their subunit composition and identify novel RNA and protein partners.

Transcriptional activation mediated by enhancer RNAs

Transcriptional activation mediated by enhancer RNAs 

A typical enhancer is located distal to its target protein coding locus (I) and depends on p300/CBP to maintain an open chromatin status. Binding of a sequence specific TF (II) recruits the Mediator complex (Med) to the enhancer and engages the RNAPII machinery (III) to initiate transcription on both strands. eRNAs are processed by Integrator (Int) to a mature form and bind to Mediator and Cohesin to help enforce a DNA looping between the enhancer and the distal gene (IV), culminating in activation of the target protein coding gene. (adapted from Gardini et al. FEBS J. 2015)