Abstract

NF-Y is a trimeric Transcription Factor -TF- which binds with high selectivity to the conserved CCAAT element. Individual ChIP-seq analysis as well as ENCODE have progressively identified locations shared by other TFs. Here, we have analyzed data introduced by ENCODE over the last five years in K562, HeLa-S3 and GM12878, including several chromatin features, as well RNA-seq profiling of HeLa cells after NF-Y inactivation. We double the number of sequence-specific TFs and co-factors reported. We catalogue them in 4 classes based on co-association criteria, infer target genes categorizations, identify positional bias of binding sites and gene expression changes. Larger and novel co-associations emerge, specifically concerning subunits of repressive complexes as well as RNA-binding proteins. On the one hand, these data better define NF-Y association with single members of major classes of TFs, on the other, they suggest that it might have a wider role in the control of mRNA production.

Highlights

  • Eukaryotic genomes contain thousands of protein coding and non-coding genes, and the understanding of their expression is a central issue in biology

  • The 728 ChIP-seq experiments of K562, HeLa-S3 and GM12878 were considered because of the availability of ChIP-seq data of NF-Y; they were divided in Not-treated (704) and Treated (24): this latter category refers to factors–including RNA Pol II–whose binding was monitored after treatment of cells with various stimuli

  • 22 ChIP-seq experiments performed with Tagged overexpressed Transcription Factors (TFs) were discarded because of the concomitant presence of ChIP-seq made with antibodies against the endogenous TF. 240 ChIP-seqs were in duplicate only in one of the two conditions, that is with Tagged proteins, or with antibodies against the endogenous TF: they were both considered

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Summary

Introduction

Eukaryotic genomes contain thousands of protein coding and non-coding genes, and the understanding of their expression is a central issue in biology. This process regulates development, differentiation and, in some cases, transformation of cells. Gene expression is initiated by production of primary RNAs by RNA Polymerases, RNA Pol II in the case of mRNAs and most regulatory non-coding RNAs. The first event driving transcriptional activation by RNA Polymerase II is the recognition and binding of Transcription Factors (TFs) to specific DNA regulatory elements (promoters and enhancers).

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