Cohesin positions the epigenetic reader Phf2 within the genome

Area of Science:

• Molecular Biology
• Epigenetics
• Genomics

Background:

• Genomic DNA is organized into chromatin by histones and DNA loops by cohesin.
• The interplay between histone modifications and cohesin in genome regulation remains largely unexplored.

Purpose of the Study:

• To investigate the functional relationship between histone modifications and cohesin-mediated genome architecture.
• To identify novel proteins that interact with cohesin and modulate its function.

Main Methods:

• Co-immunoprecipitation to identify cohesin-interacting proteins.
• Chromatin immunoprecipitation followed by sequencing (ChIP-seq) to map protein localization.
• Depletion studies using RNA interference (RNAi) to assess protein function.
• Analysis of chromatin compartments and loop structures.

Main Results:

• Phf2, a histone demethylase, was identified as a cohesin-interacting protein.
• Phf2 binds to H3K4me3 at active transcription start sites (TSSs) and co-localizes with cohesin.
• Cohesin depletion affects Phf2 localization, while Wapl and CTCF depletion alter the genome-wide distribution of both proteins.
• Phf2 depletion impacts cohesin binding at TSSs, reduces short cohesin loop formation, and expands heterochromatic B compartments.

Conclusions:

• Phf2 functions as an epigenetic reader, guided by cohesin-mediated DNA loop extrusion.
• Phf2 plays a role in recruiting cohesin to active TSSs and regulating the size of heterochromatic compartments.
• This study reveals a novel cooperativity between epigenetic mechanisms and DNA architectural proteins in eukaryotic genome regulation.