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MARGE predicts YY1 as a functional transcription factor (TF) regulating phenotype-associated genes. (a) MARGE schematic. MARGE predict functional cis-regulatory (enhancer) profiles of a given gene list, using a compendium of public H3K27ac ChIP-seq profiles. Key TFs are further predicted by associating the cis-regulatory (enhancer) profiles generated by MARGE with each of 2264 collected public TF ChIP-seq datasets. For each TF dataset, a receiver operating characteristic (ROC) curve is generated, and the area under the curve (AUC) is used to assess the association of the regulatory profile with this TF in the genome. (b) Sample genome browser snapshot of a public YY1 ChIP-seq profile (upper track) and an MARGE-predicted cis-regulatory (enhancer) profile (lower track). YY1 ChIP-seq dataset is from K562 cell line (Pope, et al., 2014). The enhancer profile is predicted from genes correlated with stiffness. (c-f) YY1 is highly enrich regardless of the phenotypic indices for MCF10A. Cumulative distributions of AUC scores for predicting all 2264 ChIP-seq datasets for different TFs’ binding (blue) and 18 datasets for YY1 binding (red). Having significantly higher AUC scores than the all-TF background, YY1 is predicted as a functional regulator of the input gene sets for cell line MCF10A. (P-value < 0.001, by K-S test.)

Journal: bioRxiv

Article Title: Integrative data analysis predicts YY1 as a Cis-regulator in the 3D Cell Culture Models of MCF10A at the Stiffness Level of High Mammographic Density

doi: 10.1101/365403

Figure Lengend Snippet: MARGE predicts YY1 as a functional transcription factor (TF) regulating phenotype-associated genes. (a) MARGE schematic. MARGE predict functional cis-regulatory (enhancer) profiles of a given gene list, using a compendium of public H3K27ac ChIP-seq profiles. Key TFs are further predicted by associating the cis-regulatory (enhancer) profiles generated by MARGE with each of 2264 collected public TF ChIP-seq datasets. For each TF dataset, a receiver operating characteristic (ROC) curve is generated, and the area under the curve (AUC) is used to assess the association of the regulatory profile with this TF in the genome. (b) Sample genome browser snapshot of a public YY1 ChIP-seq profile (upper track) and an MARGE-predicted cis-regulatory (enhancer) profile (lower track). YY1 ChIP-seq dataset is from K562 cell line (Pope, et al., 2014). The enhancer profile is predicted from genes correlated with stiffness. (c-f) YY1 is highly enrich regardless of the phenotypic indices for MCF10A. Cumulative distributions of AUC scores for predicting all 2264 ChIP-seq datasets for different TFs’ binding (blue) and 18 datasets for YY1 binding (red). Having significantly higher AUC scores than the all-TF background, YY1 is predicted as a functional regulator of the input gene sets for cell line MCF10A. (P-value < 0.001, by K-S test.)

Article Snippet: The CRISPR-cas9 technology was used to transfect MCF10A cell lines to overexpress/knockout YY1 (Santa Cruz Biotechnology, SC400295/SC409112).

Techniques: Functional Assay, ChIP-sequencing, Generated, Binding Assay

YY1 regulates ERBB2 in MCF10A monitored by fluorescent microscopy. A cross section of a multicellular system imaged with confocal microscopy. 3D colony formation is fixed at day 10 and stained. Top row shows a colony with DAPI, ERBB2, YY1 stain at 100 Pa. Bottom row shows DAPI, ERBB2, YY1, and merged signal of YY1 and ERBB2 at 1800Pa. Scale bar is Scale bar is 20 µm.

Journal: bioRxiv

Article Title: Integrative data analysis predicts YY1 as a Cis-regulator in the 3D Cell Culture Models of MCF10A at the Stiffness Level of High Mammographic Density

doi: 10.1101/365403

Figure Lengend Snippet: YY1 regulates ERBB2 in MCF10A monitored by fluorescent microscopy. A cross section of a multicellular system imaged with confocal microscopy. 3D colony formation is fixed at day 10 and stained. Top row shows a colony with DAPI, ERBB2, YY1 stain at 100 Pa. Bottom row shows DAPI, ERBB2, YY1, and merged signal of YY1 and ERBB2 at 1800Pa. Scale bar is Scale bar is 20 µm.

Article Snippet: The CRISPR-cas9 technology was used to transfect MCF10A cell lines to overexpress/knockout YY1 (Santa Cruz Biotechnology, SC400295/SC409112).

Techniques: Microscopy, Confocal Microscopy, Staining