Dynamic change of transcription pausing through modulating NELF protein stability regulates granulocytic differentiation

Xiuli Liu, Aishwarya A. Gogate, Melodi Tastemel, Venkat S. Malladi, Huiyu Yao, Kim Nguyen, Lily Jun Shen Huang, Xiaoying Bai

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

The negative elongation factor (NELF) complex is a metazoan-specific factor essential for establishing transcription pausing. Although NELF has been implicated in cell-fate regulation, the cellular regulation of NELF and its intrinsic role in specific lineage differentiation remains largely unknown. Using mammalian hematopoietic differentiation as a model system, here we identified a dynamic change of NELF-mediated transcription pausing as a novel mechanism regulating hematopoietic differentiation. We found a sharp decrease of NELF protein abundance upon granulocytic differentiation and a subsequent genome-wide reduction of transcription pausing. This loss of pausing coincides with activation of granulocyte-affiliated genes and diminished expression of progenitor markers. Functional studies revealed that sustained expression of NELF inhibits granulocytic differentiation, whereas NELF depletion in progenitor cells leads to premature differentiation toward the granulocytic lineage. Our results thus uncover a previously unrecognized regulation of transcription pausing by modulating NELF protein abundance to control cellular differentiation.

Original languageEnglish (US)
Pages (from-to)1358-1367
Number of pages10
JournalBlood Advances
Volume1
Issue number18
DOIs
StatePublished - Aug 8 2017

ASJC Scopus subject areas

  • Hematology

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