Integrating transcription-factor abundance with chromatin accessibility in human erythroid lineage commitment

整合转录因子丰度和染色质可及性以研究人类红系分化

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作者:Reema Baskar ,Amy F Chen ,Patricia Favaro ,Warren Reynolds ,Fabian Mueller ,Luciene Borges ,Sizun Jiang ,Hyun Shin Park ,Eric T Kool ,William J Greenleaf ,Sean C Bendall

Abstract

Master transcription factors (TFs) directly regulate present and future cell states by binding DNA regulatory elements and driving gene-expression programs. Their abundance influences epigenetic priming to different cell fates at the chromatin level, especially in the context of differentiation. In order to link TF protein abundance to changes in TF motif accessibility and open chromatin, we developed InTAC-seq, a method for simultaneous quantification of genome-wide chromatin accessibility and intracellular protein abundance in fixed cells. Our method produces high-quality data and is a cost-effective alternative to single-cell techniques. We showcase our method by purifying bone marrow (BM) progenitor cells based on GATA-1 protein levels and establish high GATA-1-expressing BM cells as both epigenetically and functionally similar to erythroid-committed progenitors.

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