On the NF-Y regulome as in ENCODE (2019).

Area of Science:

• Molecular Biology
• Genomics
• Transcriptomics

Background:

• NF-Y (Nuclear Factor Y) is a trimeric transcription factor known for its high-affinity binding to the CCAAT element.
• Previous studies using ChIP-seq and ENCODE data identified NF-Y binding sites and co-localization with other transcription factors (TFs).

Purpose of the Study:

• To comprehensively analyze ENCODE data over five years in K562, HeLa-S3, and GM12878 cell lines to identify novel NF-Y co-associating factors.
• To investigate the functional implications of these associations on gene expression and chromatin features.

Main Methods:

• Analysis of extensive ENCODE datasets including ChIP-seq for multiple TFs and chromatin features.
• RNA-sequencing (RNA-seq) of HeLa cells following NF-Y inactivation.
• Classification of co-associating TFs and co-factors into four distinct categories based on binding patterns.

Main Results:

• Doubled the number of identified sequence-specific TFs and co-factors associated with NF-Y.
• Identified novel co-associations, particularly with subunits of repressive complexes and RNA-binding proteins.
• Revealed positional biases in TF binding sites and significant gene expression changes upon NF-Y inactivation.
• Categorized target genes based on inferred TF associations.

Conclusions:

• NF-Y's association with major TF classes is better defined, highlighting its role in gene regulation.
• Emerging evidence suggests NF-Y plays a more extensive role in the control of mRNA production than previously understood.