HiC and Capture-HiC data

Here, through integrated multi-omics analysis, we identify TAL1 as a bona fide pioneer transcription factor that coordinates a multi-layered chromatin remodeling program essential for erythroid commitment. We demonstrate that TAL1 binds nucleosomal DNA and localizes predominantly to closed chromatin regions.

Mechanistically, TAL1 recruits the SWI/SNF chromatin remodeling complex via direct interaction with BRG1, enabling accessibility at target loci. At the level of 3D genome organization, TAL1 establishes lineage-specific chromatin loops, and its depletion disrupts long-range interactions, leading to loss of erythroid identity and aberrant activation of myeloid programs. Finally, we delineate a downstream effector pathway wherein TAL1 directly activates the chromatin remodeler BPTF and the histone modifier KMT2A, which execute complementary functions-BPTF safeguards progenitor survival while KMT2A enforces differentiation commitment.