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Comment
. 2023 Oct 9;24(10):e57927.
doi: 10.15252/embr.202357927. Epub 2023 Aug 31.

Hematopoiesis: a BETter understanding

Nirmalya Dasgupta  1 , Peter D Adams  1
Affiliations
Comment

Hematopoiesis: a BETter understanding

Nirmalya Dasgupta et al. EMBO Rep. .

Abstract

Epigenetic modifications are known to be crucial for hematopoietic stem cell (HSC) differentiation, with the BET family member BRD4 playing a vital role in this as an epigenetic reader. In this issue of EMBO reports, Yang et al (2023) demonstrate that the absence of BRD4 leads to senescence in HSCs and hematopoietic progenitor cells (HPCs), affecting the expression of crucial genes involved in myeloid and erythroid development. These data suggest that BRD4 has a protective role in preserving histone tails, thereby sustaining normal HSC/HPC functions.

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Figures

Figure 1
Figure 1. Role of BRD4 in hematopoiesis
In hematopoiesis, BRD4 maintains normal HSC/HPC functions by protecting the histone tail. However, when BRD4 is lost, this leads to H3.3 clipping. Clipped H3 (cH3) binds to senescence‐specific genes and promotes the generation of H3K27ac, H3K122ac, and H3K4me3 histone modifications. These modifications render the chromatin more accessible and promote transcription of senescence‐specific genes. Consequently, the absence of BRD4 can result in growth arrest and senescence in HSC/HPCs.
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References

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