Diversity and Complexity in Chromatin Recognition by TFII-I Transcription Factors in Pluripotent Embryonic Stem Cells and Embryonic Tissues

Aleksandr V Makeyev,Seung-Hyun Hong,Dashzeveg Bayarsaihan,Dong-Guk Shin,Pujan Joshi,Badam Enkhmandakh,Fatah Kashanchi

doi:10.1371/journal.pone.0044443

Aleksandr V Makeyev, Seung-Hyun Hong + Show 5 more

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https://doi.org/10.1371/journal.pone.0044443

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Abstract

GTF2I and GTF2IRD1 encode a family of closely related transcription factors TFII-I and BEN critical in embryonic development. Both genes are deleted in Williams-Beuren syndrome, a complex genetic disorder associated with neurocognitive, craniofacial, dental and skeletal abnormalities. Although genome-wide promoter analysis has revealed the existence of multiple TFII-I binding sites in embryonic stem cells (ESCs), there was no correlation between TFII-I occupancy and gene expression. Surprisingly, TFII-I recognizes the promoter sequences enriched for H3K4me3/K27me3 bivalent domain, an epigenetic signature of developmentally important genes. Moreover, we discovered significant differences in the association between TFII-I and BEN with the cis-regulatory elements in ESCs and embryonic craniofacial tissues. Our data indicate that in embryonic tissues BEN, but not the highly homologous TFII-I, is primarily recruited to target gene promoters. We propose a “feed-forward model” of gene regulation to explain the specificity of promoter recognition by TFII-I factors in eukaryotic cells.

Highlights

TFII-I and BEN, products of paralogous genes Gtf2i and Gtf2ird1, display a dynamic expression pattern during mouse embryo development [1][2]
The promoter Chromatin immunoprecipitation (ChIP)-chip analysis was used to identify regions bound by TFII-I and BEN in the mouse embryonic stem cells (ESCs) lines E14tg2a and Ainv15 and embryonic craniofacial tissues (ETs) derived from E10.5 mouse embryos (Fig. 1A)
We discovered that TFII-I binding sites are significantly enriched in ESCs, which is contrary to the enrichment of BEN in embryonic craniofacial tissues

Summary

Introduction

TFII-I and BEN, products of paralogous genes Gtf2i and Gtf2ird, display a dynamic expression pattern during mouse embryo development [1][2]. The SELEX procedure performed with a set of isolated I-repeats identified the core RGATTR sequence as a common DNA-binding motif for repeats 4 and 5 of BEN and for repeats 4 and 6 of TFII-I [7]. This core consensus sequence corresponds to the bona fide BEN-binding sites located in the upstream regulatory regions of Hoxc, Tnn Gsc, Scand, Cfl, Shrm and Ezh genes [4] [8][9][10][11][12]. We reported that in mouse ESCs TFII-I binds to the canonical R4 consensus in the promoters of Cfdp, Sec23a and Nsd1 [21]

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