H3 acetylation selectively promotes basal progenitor proliferation and neocortex expansion

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • C. Kerimoglu - (First author)
  • Q.L. Pham - (Author)
  • A.B. Tonchev - (Author)
  • M.S. Sakib - (Author)
  • Y. Xie - (Author)
  • G. Sokpor - (Author)
  • P.A. Ulmke - (Author)
  • L Kaurani - (Author)
  • E Abbas - (Author)
  • H Nguyen - (Author)
  • J Rosenbusch - (Author)
  • A Michurina - (Author)
  • V Capece - (Author)
  • M Angelova - (Author)
  • N Maricic - (Author)
  • B Brand-Saberi - (Author)
  • M Esgleas - (Author)
  • Mareike Albert - , Max Planck Institute of Molecular Cell Biology and Genetics (Author)
  • R Minkov - (Author)
  • E Kovachev - (Author)
  • U Teichmann - (Author)
  • RH Seong - (Author)
  • Huttner WB. - (Author)
  • HP Nguyen - (Author)
  • A Stoykova - (Author)
  • JF Staiger - (Author)
  • A Fischer - (Author)
  • T Tuoc - (Author)

Abstract

Increase in the size of human neocortex―acquired in evolution―accounts for the unique cognitive capacity of humans. This expansion reflects the evolutionarily enhanced proliferative ability of basal progenitors (BPs), including the basal radial glia and basal intermediate progenitors (bIPs) in mammalian cortex, which may have been acquired through epigenetic alterations in BPs. However, how the epigenome in BPs differs across species is not known. Here, we report that histone H3 acetylation is a key epigenetic regulation in bIP amplification and cortical expansion. Through epigenetic profiling of sorted bIPs, we show that histone H3 lysine 9 acetylation (H3K9ac) is low in murine bIPs and high in human bIPs. Elevated H3K9ac preferentially increases bIP proliferation, increasing the size and folding of the normally smooth mouse neocortex. H3K9ac drives bIP amplification by increasing expression of the evolutionarily regulated gene, Trnp1, in developing cortex. Our findings demonstrate a previously unknown mechanism that controls cortical architecture.

Details

Original languageEnglish
JournalScience advances
Volume7
Issue number38
Publication statusPublished - 17 Sep 2021
Peer-reviewedYes
Externally publishedYes

External IDs

Scopus 85115137979

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