mesc line 46c , in which the expression of gfp was driven by the endogenous sox1 gene ( sox1-gfp ) , was kindly provided by dr . austin smith ' lab . briefly , dissociated single mescs were plated onto 0.1% gelatin coated dishes and cultured in n2b27 medium at the density of 0.51    10/cm . n2b27 medium comprises 50% dmem / f12 and 50% neurobasal medium ( both from gibco ) supplemented with 1   n2 , 1   b27 ( gibco ) , 0.1% bovine serum albumin fraction v ( roche ) , 1  mm glutamine ( gibco ) , and 0.1  mm -mercaptoethanol ( gibco ) . on days 2 , 4 and 6 , cells were collected for h3 acetylation chip and hdac1 chip - seq was performed on day 2 samples ( fig . briefly , differentiated cells were cross - linked , lysed and sonicated to generate dna fragments with an average size of 200  bp . cell lysate was subjected to immunoprecipitation with antibodies against acetylated h3 or hdac1 or directly used as chip input . 1015  ng ip dna and input dna measured by qubit fluorometer ( invitrogen ) were used to construct sequencing library by chip - seq sample prep kit ( illumina ) . enriched dna sequencing was performed on hiseq 2000 or genome analyzer iix ( illumina ) . reads were mapped to mm10 using bowtie ( version 0.12.8 ) . only reads with less than two mismatches that uniquely mapped to the genome were used in subsequent analyses . signal of merged peaks was calculated by reads from chip - seq located in that region subtracting that from input , and then normalized by peak length and sequencing depth per 10 million . we defined genes bound by hdac1 if peaks were identified by macs at gene promoter region ( upstream 2.5  kb and downstream 7.5  kb of tss ) . for acetylated histone h3 chip - seq , read peaks from three neural differentiation time - points ( days 2 , 4 and 6 ) were further merged requiring adjacent distance less than 500  bp . mesc line 46c , in which the expression of gfp was driven by the endogenous sox1 gene ( sox1-gfp ) , was kindly provided by dr . austin smith ' lab . briefly , dissociated single mescs were plated onto 0.1% gelatin coated dishes and cultured in n2b27 medium at the density of 0.51    10/cm . n2b27 medium comprises 50% dmem / f12 and 50% neurobasal medium ( both from gibco ) supplemented with 1   n2 , 1   b27 ( gibco ) , 0.1% bovine serum albumin fraction v ( roche ) , 1  mm glutamine ( gibco ) , and 0.1  mm -mercaptoethanol ( gibco ) . on days 2 , 4 and 6 , cells were collected for h3 acetylation chip and hdac1 chip - seq was performed on day 2 samples ( fig . briefly , differentiated cells were cross - linked , lysed and sonicated to generate dna fragments with an average size of 200  bp . cell lysate was subjected to immunoprecipitation with antibodies against acetylated h3 or hdac1 or directly used as chip input . 1015  ng ip dna and input dna measured by qubit fluorometer ( invitrogen ) were used to construct sequencing library by chip - seq sample prep kit ( illumina ) . enriched dna sequencing was performed on hiseq 2000 or genome analyzer iix ( illumina ) . reads were mapped to mm10 using bowtie ( version 0.12.8 ) . only reads with less than two mismatches that uniquely mapped to the genome were used in subsequent analyses . signal of merged peaks was calculated by reads from chip - seq located in that region subtracting that from input , and then normalized by peak length and sequencing depth per 10 million . we defined genes bound by hdac1 if peaks were identified by macs at gene promoter region ( upstream 2.5  kb and downstream 7.5  kb of tss ) . for acetylated histone h3 chip - seq , read peaks from three neural differentiation time - points ( days 2 , 4 and 6 ) were further merged requiring adjacent distance less than 500  bp .
epigenetic modification as an intrinsic fine - tune program cooperates with key transcription factors to regulate the cell fate determination . 
 the histone acetylation participating in neural differentiation of pluripotent stem cells is expected but not well studied . here , using acetylated histone h3 chip - sequencing ( chip - seq ) , we demonstrate that the histone h3 acetylation level is gradually increased on the neural gene loci while decreased on the neural - inhibitory gene loci during mouse embryonic stem cell ( mesc ) neural differentiation . 
 we further show that histone deacetylase 1 ( hdac1 ) is essential for neural commitment by targeting nodal signaling . 
 thus , our study reveals a mechanism by which the epigenetic modification of histone acetylation / deacetylation interacts with extracellular signaling in mesc neural fate determination . 
 data were deposited in gene expression omnibus ( geo ) datasets under reference number gse66025 .