Intergenerationally Maintained Histone H4 Lysine 16 Acetylation Is Instructive for Future Gene Activation

Area of Science:

• Developmental Biology
• Epigenetics
• Genomics

Background:

• Early embryogenesis involves genome reprogramming from a quiescent to an active state before zygotic genome activation (ZGA).
• Mechanisms establishing euchromatin during this critical transition are not fully understood.

Purpose of the Study:

• To investigate the role of histone H4 lysine 16 acetylation (H4K16ac) in preparing the genome for ZGA.
• To determine the functional importance of maternal H4K16ac for embryonic development.

Main Methods:

• Studied H4K16ac maintenance from oocytes to embryos in Drosophila and mammals.
• Investigated the impact of maternal MOF acetyltransferase depletion on H4K16ac levels and gene expression.
• Assessed the effects of H4K16ac loss on RNA Pol II recruitment, 3D genome organization, and gene activation during ZGA.

Main Results:

• H4K16ac is conserved from oocytes to fertilized embryos and forms domains controlling promoter accessibility before ZGA.
• Maternal H4K16ac loss disrupts genome organization, RNA Pol II recruitment, and gene expression.
• Other histone acetylation marks cannot compensate for H4K16ac loss, and its zygotic re-expression fails to rescue viability.

Conclusions:

• Maternal H4K16ac plays an essential instructive role in priming the embryonic genome for post-ZGA gene activation.
• H4K16ac is indispensable for proper euchromatin establishment and developmental progression.