Posted in Asia-Pacific, Research

Hematopoietic/erythroid enhancers activate nearby target genes by extending histone H3K27ac and transcribing intergenic RNA

 March 18, 2023



doi: 10.1096/fj.202201891R.

Affiliations

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Yea Woon Kim et al.


FASEB J.


2023 Apr.

Abstract

Enhancers activate gene transcription remotely, which requires tissue specific transcription factors binding to them. GATA1 and TAL1 are hematopoietic/erythroid-specific factors and often bind together to enhancers, activating target genes. Interestingly, we found that some hematopoietic/erythroid genes are transcribed in a GATA1-dependent but TAL1-independnet manner. They appear to have enhancers within a relatively short distance. In this study, we paired highly transcribed hematopoietic/erythroid genes with the nearest GATA1/TAL1-binding enhancers and analyzed these putative enhancer-gene pairs depending on distance between them. Enhancers located at various distances from genes in the pairs, which was not related to transcription level of the genes. However, genes with enhancers at short distances away tended to be transcriptionally unaffected by TAL1 depletion. Histone H3K27ac extended from the enhancers to target genes. The H3K27ac extension was maintained without TAL1, even though it disappeared owing to the loss of GATA1. Intergenic RNA was highly transcribed from the enhancers to nearby target genes, independent of TAL1. Taken together, TAL1-independent transcription of hematopoietic/erythroid genes appears to be promoted by enhancers present in a short distance. These enhancers are likely to activate nearby target genes by tracking the intervening regions.


Keywords:

GATA1; TAL1; enhancers; histone H3K27ac; intergenic transcription.

References

REFERENCES

    1. Field A, Adelman K. Evaluating enhancer function and transcription. Annu Rev Biochem. 2020;89:213-234.

    1. Calo E, Wysocka J. Modification of enhancer chromatin: what, how, and why? Mol Cell. 2013;49:825-837.

    1. Spitz F, Furlong EE. Transcription factors: from enhancer binding to developmental control. Nat Rev Genet. 2012;13:613-626.

    1. Tolhuis B, Palstra RJ, Splinter E, Grosveld F, de Laat W. Looping and interaction between hypersensitive sites in the active β-globin locus. Mol Cell. 2002;10:1453-1465.

    1. Palstra RJ, Tolhuis B, Splinter E, Nijmeijer R, Grosveld F, de Laat W. The β-globin nuclear compartment in development and erythroid differentiation. Nat Genet. 2003;35:190-194.

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