Setd1a and NURF mediate chromatin dynamics and gene regulation during erythroid lineage commitment and differentiation

Ying Li, Vincent P. Schulz, Changwang Deng, Guangyao Li, Yong Shen, Betsabeh K. Tusi, Gina Ma, Jared Stees, Yi Qiu, Laurie A. Steiner, Lei Zhou, Keji Zhao, Jörg Bungert, Patrick G. Gallagher, Suming Huang

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

The modulation of chromatin structure is a key step in transcription regulation in mammalian cells and eventually determines lineage commitment and differentiation. USF1/2, Setd1a and NURF complexes interact to regulate chromatin architecture in erythropoiesis, but the mechanistic basis for this regulation is hitherto unknown. Here we showed that Setd1a and NURF complexes bind to promoters to control chromatin structural alterations and gene activation in a cell context dependent manner. In human primary erythroid cells USF1/2, H3K4me3 and the NURF complex were significantly co-enriched at transcription start sites of erythroid genes, and their binding was associated with promoter/enhancer accessibility that resulted from nucleosome repositioning. Mice deficient for Setd1a, an H3K4 trimethylase, in the erythroid compartment exhibited reduced Ter119/CD71 positive erythroblasts, peripheral blood RBCs and hemoglobin levels. Loss of Setd1a led to a reduction of promoter-associated H3K4 methylation, inhibition of gene transcription and blockade of erythroid differentiation. This was associated with alterations in NURF complex occupancy at erythroid gene promoters and reduced chromatin accessibility. Setd1a deficiency caused decreased associations between enhancer and promoter looped interactions as well as reduced expression of erythroid genes such as the adult β-globin gene. These data indicate that Setd1a and NURF complexes are specifically targeted to and coordinately regulate erythroid promoter chromatin dynamics during erythroid lineage differentiation.

Original languageEnglish (US)
Pages (from-to)7173-7188
Number of pages16
JournalNucleic Acids Research
Volume44
Issue number15
DOIs
StatePublished - Sep 6 2016

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Chromatin
Genes
Erythroblasts
Erythroid Cells
Globins
Nucleosomes
Erythropoiesis
Transcription Initiation Site
Methylation
Transcriptional Activation
Hemoglobins
Gene Expression

All Science Journal Classification (ASJC) codes

  • Genetics

Cite this

Li, Ying ; Schulz, Vincent P. ; Deng, Changwang ; Li, Guangyao ; Shen, Yong ; Tusi, Betsabeh K. ; Ma, Gina ; Stees, Jared ; Qiu, Yi ; Steiner, Laurie A. ; Zhou, Lei ; Zhao, Keji ; Bungert, Jörg ; Gallagher, Patrick G. ; Huang, Suming. / Setd1a and NURF mediate chromatin dynamics and gene regulation during erythroid lineage commitment and differentiation. In: Nucleic Acids Research. 2016 ; Vol. 44, No. 15. pp. 7173-7188.
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abstract = "The modulation of chromatin structure is a key step in transcription regulation in mammalian cells and eventually determines lineage commitment and differentiation. USF1/2, Setd1a and NURF complexes interact to regulate chromatin architecture in erythropoiesis, but the mechanistic basis for this regulation is hitherto unknown. Here we showed that Setd1a and NURF complexes bind to promoters to control chromatin structural alterations and gene activation in a cell context dependent manner. In human primary erythroid cells USF1/2, H3K4me3 and the NURF complex were significantly co-enriched at transcription start sites of erythroid genes, and their binding was associated with promoter/enhancer accessibility that resulted from nucleosome repositioning. Mice deficient for Setd1a, an H3K4 trimethylase, in the erythroid compartment exhibited reduced Ter119/CD71 positive erythroblasts, peripheral blood RBCs and hemoglobin levels. Loss of Setd1a led to a reduction of promoter-associated H3K4 methylation, inhibition of gene transcription and blockade of erythroid differentiation. This was associated with alterations in NURF complex occupancy at erythroid gene promoters and reduced chromatin accessibility. Setd1a deficiency caused decreased associations between enhancer and promoter looped interactions as well as reduced expression of erythroid genes such as the adult β-globin gene. These data indicate that Setd1a and NURF complexes are specifically targeted to and coordinately regulate erythroid promoter chromatin dynamics during erythroid lineage differentiation.",
author = "Ying Li and Schulz, {Vincent P.} and Changwang Deng and Guangyao Li and Yong Shen and Tusi, {Betsabeh K.} and Gina Ma and Jared Stees and Yi Qiu and Steiner, {Laurie A.} and Lei Zhou and Keji Zhao and J{\"o}rg Bungert and Gallagher, {Patrick G.} and Suming Huang",
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Li, Y, Schulz, VP, Deng, C, Li, G, Shen, Y, Tusi, BK, Ma, G, Stees, J, Qiu, Y, Steiner, LA, Zhou, L, Zhao, K, Bungert, J, Gallagher, PG & Huang, S 2016, 'Setd1a and NURF mediate chromatin dynamics and gene regulation during erythroid lineage commitment and differentiation', Nucleic Acids Research, vol. 44, no. 15, pp. 7173-7188. https://doi.org/10.1093/nar/gkw327

Setd1a and NURF mediate chromatin dynamics and gene regulation during erythroid lineage commitment and differentiation. / Li, Ying; Schulz, Vincent P.; Deng, Changwang; Li, Guangyao; Shen, Yong; Tusi, Betsabeh K.; Ma, Gina; Stees, Jared; Qiu, Yi; Steiner, Laurie A.; Zhou, Lei; Zhao, Keji; Bungert, Jörg; Gallagher, Patrick G.; Huang, Suming.

In: Nucleic Acids Research, Vol. 44, No. 15, 06.09.2016, p. 7173-7188.

Research output: Contribution to journalArticle

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AU - Li, Ying

AU - Schulz, Vincent P.

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AU - Shen, Yong

AU - Tusi, Betsabeh K.

AU - Ma, Gina

AU - Stees, Jared

AU - Qiu, Yi

AU - Steiner, Laurie A.

AU - Zhou, Lei

AU - Zhao, Keji

AU - Bungert, Jörg

AU - Gallagher, Patrick G.

AU - Huang, Suming

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