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Phase Separation of FOXA1 Unpacks the Condensed Chromatin to Function as a Pioneer Factor

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE231364 | GEO | 2023/12/03

REPOSITORIES: GEO

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Phase Separation of FOXA1 Unpacks the Condensed Chromatin to Function as a Pioneer Factor [ChIP-seq]

Project description:Eukaryotic DNA is packaged into chromatin in the nucleus, which restricts the binding of transcription factors (TFs) to the target DNA sites. FOXA1 functions as a pioneer TF to bind condensed chromatin and initiates the opening of local chromatin for gene expression. However, the principles of how FOXA1 recruits to and unpacks the condensed chromatin remain elusive. Here, we revealed that FOXA1 intrinsically undergoes phase separation through its N-PrLD and C-IDR regions, identified as phase separation region (PSR). Notably, the phase separation property confers FOXA1 the ability to dissolve the chromatin condensates. In addition, the DNA-binding capacity of FOXA1 contributes to its phase separation property. Further genome-wide investigation showed that FOXA1 is recruited to and unpacks the condensed chromatin by its PSR to regulate the function of breast cancer cells. This work provides a principal example of how pioneer TFs function to initiate competent chromatin states by phase separation.

2023-12-04 | GSE231361 | GEO

Phase Separation of FOXA1 Unpacks the Condensed Chromatin to Function as a Pioneer Factor [RNA-seq]

2023-12-04 | GSE231363 | GEO

Phase Separation of FOXA1 Unpacks the Condensed Chromatin to Function as a Pioneer Factor [ATAC-seq]

2023-12-04 | GSE231362 | GEO

Phase Separation of FOXA1 Unpacks the Condensed Chromatin to Function as a Pioneer Factor (NIH-3T3 cells)

2023-12-03 | GSE242240 | GEO

Phase Separation of FOXA1 Unpacks the Condensed Chromatin to Function as a Pioneer Factor

Project description:Phase Separation of FOXA1 Unpacks the Condensed Chromatin to Function as a Pioneer Factor

| PRJNA964574 | ENA

Phase Separation of FOXA1 Unpacks the Condensed Chromatin to Function as a Pioneer Factor [ATAC-seq]

Project description:Phase Separation of FOXA1 Unpacks the Condensed Chromatin to Function as a Pioneer Factor [ATAC-seq]

| PRJNA964577 | ENA

Phase Separation of FOXA1 Unpacks the Condensed Chromatin to Function as a Pioneer Factor [ChIP-seq]

Project description:Phase Separation of FOXA1 Unpacks the Condensed Chromatin to Function as a Pioneer Factor [ChIP-seq]

| PRJNA964579 | ENA

Phase Separation of FOXA1 Unpacks the Condensed Chromatin to Function as a Pioneer Factor [RNA-seq]

Project description:Phase Separation of FOXA1 Unpacks the Condensed Chromatin to Function as a Pioneer Factor [RNA-seq]

| PRJNA964578 | ENA

Phase Separation of FOXA1 Unpacks the Condensed Chromatin to Function as a Pioneer Factor (NIH-3T3 cells)

Project description:Phase Separation of FOXA1 Unpacks the Condensed Chromatin to Function as a Pioneer Factor (NIH-3T3 cells)

| PRJNA1012475 | ENA

Cooperativity of co-factor NR2F2 with Pioneer Factors GATA3, FOXA1 in promoting ER? function.

Project description:Estrogen receptor ? (ER?) drives growth in the majority of human breast cancers by binding to regulatory elements and inducing transcriptional events that promote tumor growth. ER? binding activity largely depends on access to binding sites on chromatin, which is facilitated in part by Pioneer Factors (PFs). Transcription factors operate in complexes through thousands of genomic binding sites in a combinatorial fashion to control the expression of genes. However, the extent of crosstalk and cooperation between ER? pioneer factors and more collaborative transcription factors in breast cancer still remains to be elucidated systematically. Methods: Here, we determined the genomic binding information of 40 transcription-related factors and histone modifications with ChIP-seq in ENCODE and integrated it with other genomic information (RNA-seq, ATAC-seq, Gene microarray, 450k methylation chip, GRO-seq), forming a multi-dimension network to illuminate ER? associated transcription. Results: We show that transcription factor, NR2F2 binds to most sites independently of estrogen. Perturbation of NR2F2 expression decreases ER? DNA binding, chromatin openning, and estrogen-dependent cell growth. In the genome-wide analysis, we show that most binding events of NR2F2 and known pioneer factors FOXA1, GATA3 occur together, covering 85% of the ER? binding sites. Regions bound by all the three TFs appeared to be the most active, to have the strongest ER? binding and to be enriched for the super enhancers. Conclusions: The ER? binds to pre-accessible sites containing ERE elements bound by the three transcription factors (NR2F2, FOXA1 and GATA3).The three genes were also identified to correlate with decreased metastatic potential in patient cohorts and co-regulate each other. Together, our results suggest that NR2F2 is a cofactor with FOXA1 and GATA3 in ER?-mediated transcription.

| S-EPMC6771234 | biostudies-literature

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