biostudies-literatureLiu XMHoward Hughes Medical InstituteBasic Research Program of Jiangsu ProvinceFoundation for the National Institutes of HealthNational Natural Science Foundation of ChinaNCI NIH HHS559https://www.ebi.ac.uk/biostudies/studies/S-EPMC11803071biostudies-literatureUnknown79(11)Transcriptional programming plays a key role in determining the cell state. Timely reconfiguration of chromatin structure and attenuation of pluripotent genes are required for efficient embryonic stem cell (ESC) differentiation. Here, we identify METTL3, a core N⁶-methyladenosine (m⁶A) catalyzing enzyme, as a crucial modulator of dynamic transcription and chromatin accessibility upon ESC-derived cardiac differentiation. Genome-wide analysis of chromatin-associated RNAs revealed that depletion of METTL3 failed to dramatically attenuate the transcription of pluripotent genes, as well as activate nascent cardiomyocyte-specific transcripts upon differentiation. Consistently, ATAC-seq analysis showed that loss of METTL3 markedly attenuated the dynamic alteration of chromatCellular and molecular life sciences : CMLSMETTL3 modulates chromatin and transcription dynamics during cell fate transition.PMC11803071BK20211219R21CA2279173207086855108556R21 CA22791781974527BK20190533Liu XMQian SBWang SMao YZhou JfalseMETTL3 modulates chromatin and transcription dynamics during cell fate transition.Transcriptional programming plays a key role in determining the cell state. Timely reconfiguration of chromatin structure and attenuation of pluripotent genes are required for efficient embryonic stem cell (ESC) differentiation. Here, we identify METTL3, a core N⁶-methyladenosine (m⁶A) catalyzing enzyme, as a crucial modulator of dynamic transcription and chromatin accessibility upon ESC-derived cardiac differentiation. Genome-wide analysis of chromatin-associated RNAs revealed that depletion of METTL3 failed to dramatically attenuate the transcription of pluripotent genes, as well as activate nascent cardiomyocyte-specific transcripts upon differentiation. Consistently, ATAC-seq analysis showed that loss of METTL3 markedly attenuated the dynamic alteration of chromat2022-01-01T00:00:00Z2022 Oct2025-04-04T01:35:59.526Z2025-04-04T01:35:59.526ZS-EPMC118030713626652010.1007/s00018-022-04590-x