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Buffering noise: KAT2A modular contributions to stabilization of transcription and cell identity in cancer and

Liliana Arede1, Cristina Pina2

  • 1Departments of Haematology; Genetics, University of Cambridge, Cambridge, United Kingdom.

Experimental Hematology
|November 23, 2020
PubMed

Insights

KAT2A, a histone acetyltransferase, is crucial for Acute Myeloid Leukemia (AML) stem cell identity. Its inhibition disrupts transcriptional noise, leading to leukemia cell differentiation and exhaustion.

Area of Science:

  • Molecular Biology
  • Cancer Biology
  • Epigenetics

Background:

  • KAT2A is a histone acetyltransferase identified as a vulnerability in Acute Myeloid Leukemia (AML).
  • KAT2A's loss or inhibition induces differentiation and exhaustion of leukemia stem cells.
  • KAT2A regulates transcriptional noise, promoting burst-like promoter activity and stabilizing gene expression, thereby preserving cell identity.

Purpose of the Study:

  • To investigate the specific roles of KAT2A-containing complexes, SAGA and ATAC, in gene expression stabilization.
  • To elucidate the contribution of SAGA and ATAC complexes to KAT2A's function in AML and other biological contexts.
  • To determine whether KAT2A's role in regulating transcriptional noise in AML is primarily mediated by the ATAC complex.

Main Methods:

  • Literature review of gene targets and complex requirements for SAGA and ATAC in cancer and development.
  • Analysis of KAT2A's role in transcriptional noise and gene expression stabilization.
  • Discussion of potential mechanisms for KAT2A-mediated regulation through SAGA and ATAC.

Main Results:

  • SAGA complex is suggested to regulate lineage-specific programs.
  • ATAC complex is proposed to maintain biosynthetic activity via ribosomal protein and translation-associated genes.
  • Evidence suggests KAT2A-mediated regulation of transcriptional noise in AML may involve the ATAC complex.

Conclusions:

  • KAT2A plays a critical role in preserving cell identity through transcriptional stabilization.
  • The SAGA and ATAC complexes differentially contribute to KAT2A's functions.
  • Further investigation is needed to fully understand the complex-specific contributions of KAT2A to transcriptional stability and its implications for cell identity control.

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