Ascl1 represses the mesendoderm induction in Xenopus.
Ascl1 is a multi-functional regulator of neural development in invertebrates and vertebrates. Ectopic expression of Ascl1 can generate functional neurons from non-neural somatic cells. The abnormal expression of ASCL1 has been reported in several types of carcinomas. We have previously identified Ascl1 as a crucial maternal regulator of the germ layer pattern formation in Xenopus Functional studies have indicated that the maternally-supplied Ascl1 renders embryonic cells a propensity to adopt neural fates on one hand, and represses the mesendoderm formation on the other. However, it remains unclear how Ascl1 achieves its repressor function during the activation of mesendoderm genes by VegT. Here, we performed series of gain- and loss-of-function experiments and found that: (i) VegT, the maternal mesendoderm determinant in Xenopus, is required for the deposition of H3K27ac and H3K9ac at its target gene loci during mesendoderm induction; (ii) Ascl1 and VegT antagonistically modulate the deposition of acetylated histone marks at mesendoderm gene loci; (iii) Ascl1 overexpression reduces the VegT-occupancy at mesendoderm gene loci; (iv) Ascl1 but not Neurog2 possesses a repressive activity during mesendoderm induction. These findings reveal a novel repressive function for Ascl1 in inhibiting non-neural fates during early Xenopus embryogenesis.
MOE Key Laboratory of Protein Sciences, Tsinghua University School of Life Sciences, Beijing 100084, China.
Zheying
Z
Min
MOE Key Laboratory of Protein Sciences, Tsinghua University School of Life Sciences, Beijing 100084, China.
Hao
H
Lin
MOE Key Laboratory of Protein Sciences, Tsinghua University School of Life Sciences, Beijing 100084, China.
Xuechen
X
Zhu
MOE Key Laboratory of Protein Sciences, Tsinghua University School of Life Sciences, Beijing 100084, China.
Li
L
Gao
MOE Key Laboratory of Protein Sciences, Tsinghua University School of Life Sciences, Beijing 100084, China.
Aftab A
AA
Khand
MOE Key Laboratory of Protein Sciences, Tsinghua University School of Life Sciences, Beijing 100084, China qhtaolab@tsinghua.edu.cn.
Qinghua
Q
Tao
D000107:Acetylation; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D006657:Histones / Q000378:metabolism; D008648:Mesoderm / Q000166:cytology*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology*; D014981:Xenopus / Q000196:embryology*; D029867:Xenopus Proteins / Q000235:genetics / Q000502:physiology*
D051792:Basic Helix-Loop-Helix Proteins; D006657:Histones; D009419:Nerve Tissue Proteins; D029867:Xenopus Proteins; C080088:ascl1 protein, Xenopus
Ascl1; VegT; histone modification; mesendoderm; repressor